** Women’s Health Initiative (WHI) (USA)

Field Names
Records
Coordinating Country
United States

(The Fred Hutchinson Cancer Research Center in Seattle, WA served as the WHI Clinical Coordinating Center for data collection, management, and analysis)

Region

USA

The WHI clinical trial and observational study was conducted at 40 clinical centers in 24 states and the District of Columbia:
- Alabama (Birmingham)
- Arizona (Tucson)
- California (Los Angeles, Oakland, Orange County, Sacramento, San Diego, Stanford, Torrance)
- Florida (Gainesville, Miami)
- Georgia (Atlanta)
- Hawaii (Honolulu)
- Illinois (Chicago)
- Iowa (Iowa City)
- Massachusetts (Boston, Worcester)
- Michigan (Detroit)
- Minnesota (Minneapolis)
- Nevada (Reno)
- New Jersey (Newark)
- New York (Bronx, Buffalo, Stony Brook)
- North Carolina (Chapel Hill, Greensboro)
- Ohio (Cincinnati, Columbus)
- Oregon (Portland)
- Pennsylvania (Pittsburgh)
- Rhode Island (Pawtucket)
- Tennessee (Memphis)
- Texas (San Antonio, Houston)
- Washington (Seattle)
- Wisconsin (Madison, Milwaukee)

Brief Database Description

** NOTE: Information on this database is publicly available so the database manager has declined to review this profile.

The original Women's Health Initiative (WHI) was a 15-year national health study established in 1991 by the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI) that focused on strategies for preventing heart disease, breast and colorectal cancer, and osteoporosis in postmenopausal women. The Fred Hutchinson Cancer Research Center in Seattle, WA serves as the WHI Clinical Coordinating Center for data collection, management, and analysis of the WHI. The WHI Clinical Trial and Observational Study were conducted at 40 Clinical Centers nationwide. Recruitment began in September 1993 and continued through October 1998 for the Clinical Trial; the Observational Study enrollment continued through December 1998. Close-out of the Clinical Trial occurred between October 2004 and March 2005. 

Overall, the WHI involved 161,808 women aged 50-79 from 40 clinical centers as part two major components: The randomized Clinical Trial, and the Observational Study. These studies attempted to address many of the inequities in women's health research and provide practical information to women and their physicians about hormone therapy, dietary patterns, and calcium/vitamin D supplements, and their effects on the prevention of heart disease, cancer, and osteoporosis.

WHI Extension Studies have continued follow-up of consenting participants, the first consenting participants from each of the original WHI study components for an additional five years (2005-2010) of follow-up, and the second consenting participants from the first Extension Study for an additional ten years (2010-2020). Annual updates on health outcomes are collected by mail from the participants enrolled in each Extension Study. The second WHI Extension Study from 2010 to 2020 enrolled 93,500 consenting participants from the first WHI Extension Study. As part of the second Extension, 80+ year old women were asked to consent to an In Person Visit at their homes during which additional blood samples were collected and various measurements were taken (such as blood pressure, height, weight, waist circumference, grip strength, etc.).There have also been other Ancillary studies, such as the Long Life Study using a subpopulation of the WHI cohort.  

Genetic and phenotypic data are routinely submitted to dbGaP. In 2010, the Women’s Health Initiative SNP Health Association Resource (SHARe) dataset was released on dBGaP (database of Genotypes and Phenotypes).  The dataset includes extensive phenotypic and genotypic data on 12,008 African American and Hispanic women aged 50-79 enrolled in one or more components of the WHI program.

 
The WHI Clinical Trial (N=68,132) included three overlapping components, each a randomized controlled comparison among women who were postmenopausal and aged 50-79 at randomization. Eligible women could be randomized into one, two, or all three of the Clinical Trial components:

- Hormone Therapy Trial (27,347): This component examined the effects of combined hormones or estrogen alone on the prevention of heart disease and osteoporotic fractures, and associated risk for breast cancer. Women participating in this component took hormone pills or a placebo (inactive pill) until the Estrogen plus Progestin and Estrogen Alone trials were stopped early in July 2002 and March 2004, respectively. All Hormone Therapy participants continued to be followed without intervention until close-out.

- Dietary Modification Trial (48,835): The Dietary Modification component evaluated the effect of a low-fat and high fruit, vegetable and grain diet on the prevention of breast and colorectal cancers and heart disease. Study participants followed either their usual eating pattern or a low-fat dietary pattern.

- Calcium/Vitamin D Supplementation Trial (36,282): This component evaluated the effect of calcium and vitamin D supplementation on the prevention of osteoporotic fractures and colorectal cancer. Women in this component took calcium and vitamin D pills or placebos.

Women who were ineligible or unwilling to join the Clinical Trial were invited to join the Observational Study (N=93,676). Recruitment, follow-up, and analysis for the Observational Study was concurrent with the Clinical Trial. The health of Observational Study participants was tracked over an average of eight years, but up to 12 years. Women who joined this study filled out periodic health forms and also visited the clinic three years after enrollment. Observational Study participants were not required to take any medication or change their health habits. It did, however, follow a woman's health over a long period of time.

Database Type
Longitudinal Population Database
- Drug and Diagnosis Data
Large Clinical Trial Database
Tissue/Blood and Genomic/Pharmacogenetic Database
- Genetic
- - GWAS
Other

-Observational Study

[The WHI had two major parts: A long-term randomized Clinical Trial with multiple interventions, and an Observational Study (non-interventional cohort) with regular follow-up periods.

The randomized controlled Clinical Trial enrolled 68,132 women into trials testing three prevention strategies. Eligible women could choose to enroll in one, two, or three of the trial components.
- Hormone Therapy Trials
- Dietary Modification Trial
- Calcium/Vitamin D Trial

The Observational Study component involves tracking the medical events and health habits of 93,676 women. Recruitment for the observational study was completed in 1998 and participants have been followed since.

The WHI holds a large repository of biological specimens that are available for ancillary study investigations. WHI will make available baseline and Year 3 serum, citrate plasma, EDTA plasma samples, and DNA for use by investigators who successfully compete for the Broad Agency Announcement.]

Database Source
Case Report Forms

Survey Data
Other

[Data were collected from participants via the following:
(1) Self-administered forms;
(2) Interviews: Data on participant’s past hormone use at baseline, current medications, and current supplements were collected by in-person interviews. In addition, management and safety data for Hormone Therapy and Calcium and Vitamin D participants were collected through interviews at annual visits and often by phone interviews for semi-annual contacts;
(3) Clinical measurements; and
(4) Biospecimens: The WHI holds a large repository of biological specimens that are available for ancillary study investigations. WHI will make available baseline and Year 3 serum, citrate plasma, EDTA plasma samples, and DNA for use by investigators who successfully compete for the Broad Agency Announcement.

Frequency of Data Collection
Other

[Data collection varied for each study in the Clinical Trial and Observational Study components, and also varied by type of data being collected. For example, the Medical History Update forms were completed semi-annually for all Clinical Trial participants and annually for all Observational Study participants.

Data collection at follow-up for general Clinical Trial (differs for specific trials): At years 1, 3, 6 and 9, Clinical Trial participants were also asked to bring in all their medications and vitamin supplements for an updated inventory, and electrocardiograms were obtained at years 3, 6, and 9. At the annual visit, all Clinical Trial participants had their questionnaires reviewed for potential outcomes and will have a brief physical exam. Additional measures were obtained at the first annual visit and at years 3, 6, and 9, with some elements restricted to a subsample.

Data collection at follow-up for Observational Study: Three years after enrollment into the study, all Observational Study participants were invited to a follow-up clinic visit. Before this visit they were mailed a packet of questionnaires on health habits, medical history and outcomes, as well as psychosocial and food frequency questionnaires. They were asked to bring in their current medications and supplements. At the clinic visit, they will have blood drawn, their medications and supplements will be recorded, and the following measurements will be taken: height, weight, waist and hip measurements, and blood pressure. At osteoporosis centers, bone densitometry studies and urine samples were completed for all Observational Study women every three years.

In the 2005-2010 and 2010-2015 WHI Extension Studies, participants have been followed annually.

For a full listing, select Frequency of Data Collection Table available at: https://cleo.whi.org/about/SitePages/Data%20Collection%20Procedures.aspx)]

Frequency of Data Update
Other

(Data for the original WHI and 2005-2010 Extension Study are no longer being updated; database updates for the 2010-2020 WHI Extension Study are ongoing.)

Years Covered
1993 - Present

[The periods of study are as follows:
WHI (original): 1993-2005
WHI Extension Study (first extension): 2005-2010
WHI Extension Study (second extension): 2010-2020]

Population Type
Outpatient/Non-Institutionalized

Clinical Trial Participants
[All women in WHI were aged 50-79 years and postmenopausal at the time of enrollment. The exclusion criteria varied for each study in the CT and OS components. More details can be obtained in Table 1 of: Hays J et al. The Women's Health Initiative recruitment methods and results. Ann Epidemiol. 2003 Oct;13(9 Suppl):S18-77 (available at: https://cleo.whi.org/about/Baseline%20Monograph/baseline_Recruitment.pdf)]

Patient Type
Outpatient/Non-Institutionalized

Clinical Trial Participants

[All women in WHI were aged 50-79 years and postmenopausal at the time of enrollment. The exclusion criteria varied for each study in the Clinical Trial and Observational Study components. More details can be obtained in Table 1 of this article: Hays J et al. The Women's Health Initiative recruitment methods and results. Ann Epidemiol. 2003 Oct;13(9 Suppl):S18-77 (available at: https://cleo.whi.org/about/Baseline%20Monograph/baseline_Recruitment.pdf)]

Date of Last Update

[The original WHI study period (1993-2005) and the first WHI Extension Study (2005-2010) are now closed. The second WHI Extension Study (2010-2020) is currently ongoing;
This profile was updated for the B.R.I.D.G.E. TO DATA site on June 30, 2020.]

Field Names
Records
Database Population Size
<200,000

 
[Overall there were 161,808 participants. The study population for each component is as follows:
Clinical Trial = 68,132
Observational Study = 93,676
Extension 1 = 115,406 (71.3% of original WHI participants)
Extension 2 = 93,500 (57.8% of original WHI participants)]

Active Population Size
<200,000

[Currently, the WHI Extension Study 2 is ongoing, and includes 93,500 participants in the database (57.8% of the original study population)]

Annual Change in Population
N/A

(Not applicable)

Sample Weights - Extrapolation Factors
No
Final Population Size
N/A

(161,808 is the final total population size of the WHI study; however, with each Extension Study or Ancillary Study, the population size decreases.)

Field Names
Records
Age of Patients at Data Collection
Yes

(Age, Age group, and Age at menopause were collected)

Approximate Percentage of Participants <18 years and those >65 years

<18 years = 0%
>60 years = 66.9%

[50 - 54 yrs N=21,570 (13.3%)
55 - 59 yrs N=31,983 (19.8%)
60 - 69 yrs N=72,588 (44.9%)
70 - 79 yrs N=35,667 (22.0%)
Total: 161,808]

Gender Data
Yes

(Females only)

Percentage of Males/Females

Males = 0%
Females = 100%

Ethnicity / Race Data
Yes

Ethnicity/Race categories include:
- American Indian or Alaskan Native N=713 (0.4%)
- Asian or Pacific Islander N=4,190 (2.6%)
- Black or African-American N=14,618 (9.0%)
- Hispanic/Latino N=6,484 (4.0%)
- White (not of Hispanic origin) N=133,541 (82.5%)
- Other N=1,849 (1.1%)
- Missing N=413 (0.3%)
Total: 161,808

An Addendum form with more specific questions on race/ethnic group was completed by 137,732 participants, which additionally listed various Asian races (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and Pacific Islanders (Hawaiian Native, Guamian/Chamorro, Samoan).

Additionally, preferred language (English/Spanish) was also obtained.

Geographic Location

USA

The WHI clinical trial and observational study was conducted at 40 clinical centers in 24 states and the District of Columbia:
- Alabama (Birmingham)
- Arizona (Tucson)
- California (Los Angeles, Oakland, Orange County, Sacramento, San Diego, Stanford, Torrance)
- Florida (Gainesville, Miami)
- Georgia (Atlanta)
- Hawaii (Honolulu)
- Illinois (Chicago)
- Iowa (Iowa City)
- Massachusetts (Boston, Worcester)
- Michigan (Detroit)
- Minnesota (Minneapolis)
- Nevada (Reno)
- New Jersey (Newark)
- New York (Bronx, Buffalo, Stony Brook)
- North Carolina (Chapel Hill, Greensboro)
- Ohio (Cincinnati, Columbus)
- Oregon (Portland)
- Pennsylvania (Pittsburgh)
- Rhode Island (Pawtucket)
- Tennessee (Memphis)
- Texas (San Antonio, Houston)
- Washington (Seattle)
- Wisconsin (Madison, Milwaukee)

Date of Birth Recorded
Yes

However, these data are not released to researchers; instead, age data can be used

Death Recorded
Yes

 
Death data are collected in the Report of Death form:
- Death,
- Date of death,
- Cause of death, and
- Method of adjudication for cause of death.

All dates in the study cannot be reported directly, including date of death; however, they are converted to 'days from enrollment'.

Availability of death certificate / autopsy information
No
Other Demographic Data
Yes

 
Socioeconomic data include the following:
- Education;
- Employment status, and occupation (for participants and participants' partners);
- Marital status;
- Total family income;
- Insurance coverage;
- Service in armed services;
- Direct family members (# siblings, etc.);
- Social support, social integration, social strain, care giving; optimism, negative emotional expressiveness, hostility, etc.;
- Daily life items (quality of life, symptoms, life events, depression, sleep disturbance, urinary incontinence, sexual functioning);
- Religious affiliation;
- State of residence history;
- US region of birth;
- Parents' birthplace;
- Lived on a farm;
- Age at first paid work;
- Life events;
- Etc.

Field Names
Records
Physician ID
Yes

Captured information includes: Clinical Center ID, Exam by, Report by, and Referral

Physician Specialty
Yes

For diagnosis relating to medical events, an adjudicator code is used (e.g., Report of Cardiovascular Outcomes)

Pharmacy ID
No
Field Names
Records
Diagnosis Data
Yes

All WHI clinical outcomes were identified by self-reporting on the routine Form 33 - Medical History Update administered semi-annually to Clinical Trial participants, and annually to Observational Study participants. Those participants who reported a potential WHI-defined outcome were then contacted by mail or phone and a Form 33D – Medical History Update (Detail) - was completed to obtain more specific information on newly diagnosed health conditions or recent procedures.

Investigation of potential WHI clinical outcomes depended on the type of outcome, the participant’s study component, and whether or not the outcome was a first versus a recurrent event. A documentation set was defined for each type of WHI clinical outcome, and these medical records were used for adjudication.

The following were the outcomes of interest:
- Cardiovascular (Coronary heart disease, Stroke, Congestive heart failure, Angina, Peripheral vascular disease, Carotid artery disease, Coronary revascularization);
- Cancer (Breast cancer, Endometrial cancer, Colorectal cancer, Ovarian cancer, Other cancers, Total cancers);
- Fractures (Hip, Other fractures); and
- Other (Pulmonary embolism, Deep vein thrombosis, Diabetes Mellitus requiring therapy, Death from any cause).

Additionally, reproductive history, quality of life data, and cognitive assessments were also collected.

Diagnoses Coded
ICD-9-CM

ICD-O-2
Other
[Diagnoses are recorded as full-text or questionnaire responses. Diagnoses are also obtained from hospital discharge records by physicians at the clinic centers, and recorded as ICD-9-CM codes. During adjudication, cancer diagnoses were recorded using both ICD-O-2 and SEER EOD (Extend of Disease).]

Diagnoses: Date Parameters
1993 - Present

[The periods of study are as follows:
WHI (original): 1993-2005
WHI Extension Study (first extension): 2005-2010
WHI Extension Study (second extension): 2010-2020]

Diagnoses: Maximum Number of Codes Allowed
Varies

(Diagnosis data varies by questionnaire/interview or clinical form)

Physical Examination Findings
Yes

Physical measurements are/were noted (height, weight, blood pressure, heart rate, waist and hip circumference)

Birth Defect Data
No

There are no specific questions on birth defects. However, the following related information is captured:

- Gynecological and pregnancy data collected include: Age at menarche, history of menstrual irregularity and amenorrhea, history of menopausal symptoms, history of pregnancy, pregnancy outcomes, infertility; history of breast feeding, and history of gynecologic & breast surgeries.

- Birth-related questions include: Birth weight, birth status, and breast feeding at birth.

Cancer Data
Yes

Data on the following cancers were specifically obtained:
- Breast cancer,
- Endometrial cancer,
- Colorectal cancer,
- Ovarian cancer,
- Other cancers, and
- Total cancers.
As with other outcomes of interest, the cancers developing after study start date were adjudicated by a clinician. Additional data included confirmation method (e.g., histology), sub-classification, reporting source, SEER summary stage, and tumor marker assay (e.g., estrogen receptor, progesterone receptor, HER-2/Neu)

Infectious Disease Data
No
Environmental Exposures
Yes

Data on non-medical exposures include:
- History of insecticide exposure;
- History of living with pets;
- History of computer use (frequency, duration);
- History of hand-held hair dryer use (frequency, duration);
- History of the use of powders in genital area or on sanitary napkins;
- History of diaphragm use;
- History of electric blanket use;
- Exposure to foods and beverages (e.g., artificial sweeteners);
- Sunlight exposure;
- Video and video display terminal exposure;
- Lived with smoker as a child;
- Use of hair dyes;
- Lived on a farm.

Behavioral Data Elements
Yes

Behavioral data include:
- Personal habits (coffee/tea consumption, smoking history, alcohol history, weight change, special diets, history of physical activity and exercise (frequency, duration, hours sitting, hours doing heavy chores);
- Thoughts and feelings (social support, social integration, care giving, social strain, optimism, negative emotional expressiveness, hostility);
- Daily life items (quality of life, symptoms, life events, depression, sleep disturbance, urinary incontinence, sexual functioning);
- Cognitive assessment (expanded mini mental status examination);
- Food/Beverage consumption (food frequency);
- Diet/Nutrition (e.g., recent use of fats or oils, recent wine consumption);
- Care-giving responsibilities;
- Sleep patterns.

Field Names
Records
Procedure Data
Yes

These data are self-reported as well as collected from the clinical center physicians who obtain patient hospital discharge records

Procedures Coded
ICD-9-CM
Other

[Procedures that are self-reported are recorded in full-text, and those obtained from hospital discharge records are provided as ICD-9-CM procedure codes (if available)]

Number of Procedures Coded
Varies
Procedure Date Parameters
1993 - Present

[The periods of study are as follows:
WHI (original): 1993-2005
WHI Extension Study (first extension): 2005-2010
WHI Extension Study (second extension): 2010-2020]

Laboratory Information
Yes

Laboratory tests include:
- Pelvic exams,
- Endometrial aspiration,
- Transvaginal uterine aspiration,
- Clinical breast exam,
- Mammogram,
- Bone density scan,
- Electrocardiogram (ECG),
- Functional status (e.g., grip strength),
- Pap smear,
- Blood tests,
- Urine tests,
- Tests done for diagnosis adjudication (e.g., pathology/histology for cancers),
- Biomarker tests (glucose, insulin, lipids, CRP, and creatinine),
- Genotyping data (limited and de-identified), and
- Biospecimen collection.

Field Names
Records
Drug Data
Yes: Prescription & OTC

Other
A list of current medications and supplements used are recorded, including duration of use (days and years). Some medications and supplements are of particular interest to the study initiatives and have questionnaires specific to them, e.g., hormone replacement therapy, use of supplements, and medications for breast health.

Drug Date Parameters
1993 - Present

[The periods of study are as follows:
WHI (original): 1993-2005
WHI Extension Study (first extension): 2005-2010
WHI Extension Study (second extension): 2010-2020]

Drug Regimen & Route
No

However, this information can be obtained from the NDC data

Drug Manufacturer
No

However, this information can be obtained from the NDC data

Drug Dosage
No
Drug Days Supply
Yes

In some cases, the number of pills/week are captured

Drug Coding System: Maximum Number
Unlimited

NOTE: This information also varies based on the specific questionnaire

Drug Coding System: Primary
NDC

(All current medications are recorded using NDC)

Drug Coding System: Other
Other

[When possible, each reported current medication is also classified using the NDC's directory of the therapeutic drug class(es), and codes are assigned to medications. Additionally, the breast health medication forms contain a drug inventory list specific to breast cancer medications (e.g., tamoxifen, raloxifene, toremifene, etc.)]

Drug Generic Name
Yes
Drug Additional Information
Yes

Additional drug data captured are:
- Adherence to study medications (intervention in WHI Clinical Trial),
- Changes in medication that occur, and
- Reason for medication change (e.g., intolerance, side effects, barriers due to insurance coverage, physician prescribing, inconvenience, etc.).

Field Names
Records
Biobank Type
Other

** NOTE: Information on this database is publicly available so the database manager has not reviewed this profile.

Clinical trial biorepository: WHI holds a large repository of biological specimens collected from WHI participants at various times over the past 20 and more years.

Specimens collected from WHI participants are maintained in a biorepository in Rockville, MD. The sample inventory is tracked via a WHI Specimen Tracking database, which includes variables associated with the specimens, such as number of fasting hours before blood draw, extraction and quantitation method, and number of freeze/thaw cycles. All biospecimens collected from WHI participants are available for use by Ancillary Studies based on scientific merit. To access WHI biospecimens, investigators must have an approved and funded ancillary study.

Human Specimen
- Blood: Serum, Plasma, Red blood cells, Buffy coat; counts for White blood cells, hematocrit, hemoglobin and platelets
- Other body fluids: Urine for the bone mineral density patient subset
- RNA for the Long Life Study patient subset

(Buffy coat samples selected for testing at the WHI central lab and are not available to researchers)

Blood Type
No
Biomarkers
Yes

Biomarker data derived from WHI core funds are available as soon as they are ready; those derived from ancillary or BAA studies are available after study’s first publication or >1 year past end of funding period. Some participants had multiple test results of the same biomarker from different studies.
Labs and/or assay methods may vary from one study to another. Biomarker sample not representative of the WHI population. Over 600 biomarkers have been tested:
Estrone (E1), 16-alpha-hydroxy
Estrone (E1), 16-alpha-hydroxy
16-alpha-hydroxyestrone-H2O
16-alpha-hydroxy estradiol
16-alpha-hydroxy estradiol-H2O
17-beta-estradiol - H20
Estrone (E1), 2-hydrox
24,25-Epoxycholesterol
24-Hydroxycholesterol
24-Oxocholesterol
25-Hydroxycholesterol
27-hydroxycholesterol
2-methoxyestrone
2-methoxyestradiol-H2O
2-hydroxyl-3-methoxyestrone
2-hydroxyl-3-methoxyestradiol
2-hydroxyl-3-methoxyestradiol-H2O
2-hydroxyestrone-1(4)-N-acetylcysteine
2-hydroxyestrone-1(4)-glutathione
2-hydroxyestrone-1-Cysteine
2-hydroxyestrone-4-Cysteine
2-hydroxyestrone-6-N3Adenine
2-hydroxyestradiol-1(4)-glutathione
2-hydroxyestradiol-1-Cysteine
2-hydroxyestradiol-1-N-acetylcysteine
2-hydroxyestradiol-4-Cysteine
2-hydroxyestradiol-4-N-acetylcysteine
2-hydroxyestradiol-6-N3Adenine
3-Hydroxyanthranilic acid
3-Hydroxykynurenine
Extractable Nuclear Antigen - Anti dsDNA >30
5a-androstane-3a,17b diol-17-glucuronide
5a-androstane-3a,17b diol-3-glucuronide
4beta-Hydroxycholesterol
4-methoxyestrone
4-methoxyestradiol-H2O
4-hydroxyestrone-1-N3Adenine
4-hydroxyestrone-1- N7Guanine
4-hydroxyestrone-2-Cysteine
4-hydroxyestrone-2-N-acetylcysteine
4-hydroxyestrone-2-glutathione
4-hydroxyestradiol-1-N3Adenine
4-hydroxyestradiol-1- N7Guanine
4-hydroxyestradiol-2-Cysteine
4-hydroxyestradiol-2-N-acetylcysteine
4-hydroxyestradiol-2-glutathione
5,6alpha-Epoxycholesterol
5,6beta-Epoxycholesterol
6alpha-Hydroxycholesterol
7alpha-Hydroxycholesterol
7alpha,27-hydroxycholesterol
Anti-cyclic Citrullinated Peptide pos/neg code
Alpha-1-Antitrypsin
alpha-2-Macroglobulin (a2M)
Lp-LPA2 Lipoprotein Activity
Alpha-Carotene
ADAM metallopeptidase
Androstanedione
Adiponectin
Adiponectin, heavy molecular weight
Asymmetric dimethylarginine
Androsterone
Androsterone-glucuronide
Alpha-Fetoprotein
Apolipoprotein A-I
Aluminum 27
Albumin
ANA Fluorescence
antinuclear antibodies pos/neg code
ANA positive/negative at 80
ANA positive/negative at 160
ANA positive/negative at 320
ANA Titer Pattern
ANA Titer Result
Androstenedione
Anthranilic acid
Activated Protein C-Endogenous Thrombin Potential
Apolipoprotein(a)
Apolipoprotein A1
Apolipoprotein A1 CIT
Apolipoprotein A-II
Apolipoprotein B
Apolipoprotein C-I
Apolipoprotein C-III
Apolipoprotein E
Apolipoprotein E 277-296 cit sm-2 cyclic
Apolipoprotein E CIT
Apolipoprotein H
Amyloid Precursor Protein
Arginine
Arsenic 75
All-trans retinol
ATIII
Tocopherol, alpha
Tocopherolacetate, alpha
Beta 2 microglobulin
Barium 137
Basophil Count
Basophil %
Beta-Carotene
Beta-carotene, 13cis
Beta-carotene, 9cis
Beta-Carotene, all trans
Beta-Cryptoxanthine
brain derived neurotrophic factor
Beryllium 9
Betaine
Biglycan 247-266 cit sm-1 cyclic
Bisphenol-A Bound (Conjugated)
Bisphenol-A Free (Unconjugated)
BP-A Total
C-peptide
Cancer antigen 125
Cancer Antigen 19-9
Calcium 44
CagA antibodies
Calcitonin
CCL19 MIP3b
CCL20 MIP3a
CCP
Cadmium 111
Cadmium 111 (below reporting limit imputed)
Cadmium 114
CD 40 antigen
CD40 Ligand
Cerium 140
carcinembryonic antigen
Choline
Clusterin 231-250 cit sm cyclic
carboxymethyl-lysine advanced glycation end products
Cobalt 59
Complement C3
Cotinine
Chromium 52
Creatinine
Creatine Kinase-MB
C-reactive protein (high sensitivity)
Cryptoxanthin
Cryptoxanthine (alpha + beta)
Caesium 133
Cutaneous T-cell-attracting chemokine
C-Terminal Telopeptide of Type I Collagen
Copper 63
CXCL11 I-TAC
Chemokine (C-X-C motif) ligand 13
CXCL6 GCP2
CXCL9 MIG
Cysteine
Cystathionine
Cystatin-C
D-dimers
Dehydroepiandrosterone
Dehydroepiandrosterone sulfate
Dehydroepiandrosterone sulfate (SO4)
Dihydrotestosterone
Dihydrotestosterone-sulfate
dihydrophylloquinone
Dimethylglycine
Tocopherol, delta
Epstein-Barr Virus to early D Antigen, IgG
Epstein-Barr Virus Antibody to Nuclear Antigen, IgG
Epstein-Barr Virus Antibody to Viral Capsid Antigen, IgG, IgG
Epithelial-Derived Neutrophil-Activating Protein 78
Epidermal Growth Factor
Extractable Nuclear Antigen - Anti dsDNA text
Extractable Nuclear Antigens - Anti-Ribonuclear protein antibodies
Extractable Nuclear Antigents - Anti-Smith antibodies
Extractable Nuclear Antigens - Anti-Ro antibodies
Extractable Nuclear Angiens - Anti-La antibodies
Endothelin-1
enolase 1
enolase 1A cyclic
EN-RAGE
Eosinophil Count
Eosinophil %
Eotaxin
Erythropoietin
E-Selectin
Estradiol, bioavailable (%)
Estradiol (E2)
Estradiol (E2), 16-keto
Estradiol (E2), 2-methoxy
Estradiol (E2), 2-methoxy-unconjugated
Estradiol (E2), 2-hydroxy
Estradiol (E2), 4-methoxy
4-hydroxyestradiol
Estradiol (E2), unconjugated
Estradiol, bioavailable
Total Estradiol Vitros Assay
Estrone (E1)
Estrone (E1), 2-methoxy
Estrone (E1), 2-methoxy-unconjugated
2-hydroxyestrone
Estrone, 3- methyl ether-hydroxy
Estrone (E1), 4-methoxy
Estrone (E1), 4-hydroxy
Estrone (E1), unconjugated
Estriol (E3)
Estriol (E3), 16-epi
Estriol (E3), 17-epi
Estriol (E3), unconjugated
Estrone sulfate (E1S)
Etiocholanolone-glucuronide
Prothrombin fragment 1+2
Factor VII
Factor VII Ag (antigen)
Factor VII:C (activity)
Factor VIII Activity
FIX Conc
Myristic Acid FA 14:0 (Tetradecanoic Acid)
Pentanoic Acid FA 15:0 (Pentadecylic Acid)
Palmitic Acid FA 16:0 (Hexadecanoic Acid)
FA Palmitoleic Acid (Hexadecenoic Acid)
Palmitelaidic Acid FA 16:1T
FA Margaric Acid 17:0 (Hexadecanoic Acid)
Stearic Acid FA 18:0 (Octadecanoic Acid)
Vaccenic Acid FA 18:1n-7 (11-Octadecenoic Acid)
Oleic Acid FA 18:1n-9 (9-Octadecenoic Acid)
FA 18:1T-1
FA 18:1T-2
FA 18:1T-3
FA 18:1T-4
FA 18:1T-5 Elaidic Acid
Linoleic Acid FA 18:2N-6 (9,12-Octadecadienoic Acid)
FA 18:2TT Linelaidic Acid
Alpha Linolenic Acid FA 18:3N-3 (9,12,15-Octadecatrienoic Acid)
Gamma Linolenic Acid FA 18:3N-6 (6,9,12- Octadecatrienoic Acid)
Eicosanoic Acid FA 20:1N-9 (Gondoic Acid)
Eicosadienoic Acid FA 20:2N-6 (Dihomolinoleic Acid)
FA Eicosatrienioc Acid (dihomo gamma linolenic acid - DHGLA)
FA Eicosatetraenoic Acid n3
Arachidonic Acid FA 20:4N-6 (5,8,11,14-Eicosatetraenoic Acid)
Eicosapentanoic Acid FA 20:5N-3 (Timnodonic Acid)
FA Adrenic Acid (aka Docosatetranoic Acid)
Docosapentanoic Acid FA 22:5N-3 (Clupanodonic Acid)
Docosapentanoic Acid FA 22:5N-6
Docosahexanoic Acid FA 22:6N-3 (Cervonic Acid)
Docosapentanoic Acid FA 22:5N-6
Docosahexanoic Acid FA 22:6N-3 (Cervonic Acid)
Nervonic Acid
Fatty Acid-Binding Protein, heart
FasLigand
Estradiol, free (non-protein bound)
Iron 56
Ferritin
Fibroblast Growth Factor basic
Fibrinogen
Fibrinogen A-CIT
Fibrinogen A 211-230 cit sm cyclic
Fibrinogen A 41-60 cit3 cyclic
Fibrinogen A 556-575 cit sm cyclic
Fibrinogen A 616-635 cit3 snall cyclic
Filaggrin 48-65 cit2 v1 cyclic
Folate
Folate, RBC
Free (non-protein bound) testosterone
bioavailable (non-SHBG bound) testosterone
Granulocyte Colony Stimulating Factor
Growth hormone
Ghrelin
Glucose
Glyc A Protein
Glyc B Protein
Glycine
Granulocyte-macrophage colony-stimulating factor
interleukin 6 signal transducer (gp130, oncostatin M receptor)
Tocopherol, gamma
H2A/a 62-81cit sm2 cyclic
H2B/a 62-81cit cyclic
Haptoglobin phenotyping
Hepatitis B core antigen antibody
Hepatitis B core antigen antibody OD
Hepatitis B surface antigen
Hepatitis B surface antigen OD
Human Chorionic Gonadotropin beta
Hematocrit
Hepatitis C virus
Hepatitis C virus OD
Large HDL Particles
Medium HDL Particles
Small HDL Particles
High-density lipoprotein-2
High-density lipoprotein-3
High-density lipoprotein cholesterol
HDL Particles Total
HDL Size
HE4 Serum marker
HE4 Serum marker (MFI)
Hemoglobin A1c from RBC
Hemoglobin
Hepatocyte growth factor
Histones 2B-CIT
Homoarginine
Homocysteine
Haptoglobin
helicobacter pylori
helicobacter positive/negative
HSP60
Hu 6Ckine
Hu Adiponectin
Hu Adipsin
Hu BCA-1
Hu CRP
Hu CTACK
Hu EGF
Hu ENA-78
Hu Eotaxin
Hu Eotaxin-2
Hu FGF-2
Hu Fractalkine
Hu G-CSF
Hu GMCSF
Hu Gro
Hu IL-10
Hu IL-12p70
Hu IL-13
Hu IL-16
Hu IL-17a
Hu IL-1b
Hu IL-1ra
Hu IL-21
Hu IL-23
Hu IL-3
Hu IL-33
Hu IL-4
Hu IL-5
Hu IL-6
Hu IL-7
Hu IL-8
Hu IP-10
Hu Lipocalin-2 NGAL
Hu MCP-1
Hu MCP-2
Hu MCP-4
Hu MDC
Hu MIP-1b
Hu MIP-1d
Hu MIP1a
Hu MIP3a
Hu PAI-1
Hu Resistin
Hu SAA
Hu SAP
Hu SCF
Hu SDF-1a+b
Hu TARC
Hu TGF-a
Hu TNF-b
Hu TNFa
Hu TPO
Hu TRAIL
Hu TSLP
Hu VEGF
Inter-Cellular Adhesion Molecule 1
IDL Particle
Interferon, gamma
Immature Granulocyte Count
Immunoglobulin A
Immunoglobulin E
Immunoglobulin M
Immature Granulocyte Fraction
IGF-I Total
Insulin growth factor 2
Insulin growth factor 1
IGF binding protein-1
IGF binding protein-2
IGF binding protein-3
IGF binding protein-4
IGF binding protein-6
IGF Free
Interleukin 10
Interleukin 12p40
Interleukin 12p70
Interleukin 13
Interleukin 15
Interleukin 16
Interleukin 17
Interleukin 18
Interleukin 1, alpha
IL-1Beta (interleukin)
Interleukin 1 receptor, type 2
Interleukin 1 receptor antagonist
Interleukin 2
Interleukin 23
IL-29 IFNl1
Interleukin 3
Interleukin 4
Interleukin 5
Interleukin 6
Interleukin 6, soluble receptor
Interleukin 7
Interleukin 8
Insulin
Potassium 39
Kynurenine
Kynureninic acid
Large LDL Particles
Medium Small LDL Particles
Small LDL Particles Total
Very Small LDL Particles
Lipo-LDL1
Lipo-LDL2
Lipo-LDL3
Lipo-LDL4
Lipo-LDL5
Lipo-LDL6
Lipo-LDL7
Low-density lipoprotein cholesterol
LDL Particles Total
LDL Size
LDL Cholesterol (total)
Leptin receptor
Leptin
Galectin-3 binding protein
Lipo-HDL
Lithium 7
lipoporotein insulin resistance score
Apolipoprotein (a)
Leucine-rich alpha-2-glycoprotein 1
Lagtime-APC
lymphocyte transforming factor
Lutein, all trans
Lutein cis isomer 1
Lutein cis isomer 2
Lutein cis isomer 3
Lycopene
Lycopene, 13 cis
Lycopene, 15 cis
Lycopene, 5 cis
Lycopene, 9 cis
Lycopene, total (trans + cis)
Lycopene, all trans
Lymphotactin
Lymphocyte Count
Lymphocyte %
Lutein and Zeaxanthin
Microtubule-associated protein
Mean Corpuscular Hemoglobin
Mean Corpuscular Hemoglobin Concentration
mono-chemotactic protein 1
mono-chemotactic protein 3
Mean Corpuscular Volume
Macrophage-Derived Chemokine
Melatonin, 6-sulfatoxy-creatinine adjusted
Methionine
Methionine sulfoxide
Magnesium 25
Lipo-MIDA
Lipo-MIDB
Lipo-MIDC
Macrophage Inflammatory Protein-1 alpha
Macrophage Inflammatory Protein 1 Beta
Methylmalonic Acid
Matrix metalloproteinase 2
Matrix metalloproteinase 3
Matrix metalloproteinase 7
Matrix metalloproteinase 9
Manganese 55
Molybdenum 95_Low Rate
Molybdenum 95_Medium Rate
Monocyte Count
Monocyte %
Mean Platelet Volume
Mesothelin
Mesothelin (MFI)
Monounsaturated Fatty Acids summary
Myeloperoxidase
Myoglobin
Sodium 23
Nicotinic acid
Nicotinamide
Normalized APC sensitivity ratio
Neopterin
Neutrophil Count
Neutrophil %
Nerve Growth Factor
Nickel 60
Nidogen 1
Non-HDLC
Neuron Specific enolase
Osteoprotegerin
Phosphorous 31
Pyridoxal-5'-phosphate (Vit B6)
Plasminogen Activator Inhibitor 1
PAI-1 Antigen
Plasmin-anti-plasmin
Pregnancy-Associated Plasma Protein A
Lead 208
Platelet Distribution Width
Pepsinogen 1
Pepsinogen 2
Aminoterminal procollagen extension propetide pyruvate kinase type M2
Pyridoxal
PLAC is also know as LP-PLA2 (lipoprotein-associated phospholipase A2)
Platelet Count
Pyridoxine
PPBP
peptidylprolyl isomerase A
Prostatic Acid Phosphatase
Prothrombin antigen
N-terminal prohormone brain natriuretic peptide
Progesterone
Proinsulin
Prolactin
Protein C
Protein S Total
Protein S Free
Prostate-Specific Antigen, Free
Platinum 195
Parathyroid Hormone
Polyunsaturated Fatty acids summary
Pyridoxic Acid
Quinolinic acid
T-Cell-Specific-Protein RANTES
Red Blood Cell Count
Red Cell Distribution Width - Coefficient of Variation %
Red Cell Distribution Width - Standard Deviation
Resistin
Reticulocyte Count
Reticulocyte %
Retinol
retinyl palmitate
Rheumatoid factor pos/neg code
Amyloid A, serum
Serum Amyloid P-Component
Sarcosine
Antimony 121
Soluble CD23
Soluble CD27
Soluble CD30
Soluble CD44
Stem Cell Factor
Symmetric dimethylarginine
Selenium 82
sEGFR
Selenium
Serine
Saturated Fatty Acids summary
Soluble Fas
Serum Glutamic Oxaloacetic Transaminase
sgp130
Sex Hormone Binding Globulin
Soluble intracellular adhesion molecule
sIL-4R
sIL-6R
sILRII
Streptomyces Lividans Plasmid 1 (normalized)
Streptomyces Lividans Plasmid 1
Tin 118_Low Rate
Tin 118_Medium Rate
T7-Tag fusion
Strontium 88
Soluble receptor for advanced glycation end products
sRANKL
serotransferrin
sTNFRI
sTNFRII
sVEGFR2
sVEGFR3
Thyroxin, free (freeT4)
Thrombin activatable fibrinolysis inhibitor concentration
Thyroxine-Binding Globulin
Total Cholesterol
calculated Cholesterol/HDL
Absolute telomere length
Telomere relative T/S ratio
Telomere Linearized delta Ct
Telomere linearized delta delta Ct (ddCt)
TF
TFPI activity
TFPI, free
Total TFPI
Thrombopoietin
Thrombospondin-1
TIMP-1
Thallium 205
Trimethylamine N-oxide
Tumor necrosis factor Alpha
Tumor Necrosis Factor beta
Tumor necrosis factor receptor 1
Tumor necrosis factor receptor 2
Tissue type plasminogen activator
Thyroid peroxidase autoantibodies
Triglyceride
Tryptophan
Thyroid Stimulating Hormone
Testosterone
Transthyretin
Uranium 238
Creatinine (urine)
Vanadium 51
Vascular cell adhesion molecule-1
Vascular endothelial growth factor
Vimentin - CIT
vimentin 58-77 cit 3 cyclic
Total Vitamin D, 25-Hydroxy
Vitamin D2, 25-Hydroxy
Vitamin D3, 25-Hydroxy
Vit D binding protein
Lipo-VLDL
Very low density lipoprotein cholesterol
Large VLDL/Chylomicron Particles
Medium VLDL Particles
Small VLDL Particles
VLDL/Chylomicron Particle ConcentrationParticles Total
VLDL Size
VLDL/Chylomicron tryiglyceride
Vitamin B12
Vitamin B2 (riboflavin)
Vitamin K (phylloquinone)
von Willebrand Factor activity or concentration
Tungsten 184
White Blood Cell Count
Xanthurenic acid
Zeaxanthin
Zeaxanthin cis isomer
Zinc 66

Patient ID
Barcode

Other unique identifier
Each blood sample contains a label with a printed 6-digit blood sample number plus a 2-digit cryovial number as well as a barcode. This label links the blood samples to the participant ID.

Number of Samples
Yes

Some participants had multiple test results of the same biomarker from different studies. Labs and/or assay methods may vary from one study to another. Some biomarkers had longitudinal measures. Biomarker sample not representative of the WHI population.

Frequency of Sample Collection
Some biomarkers had longitudinal measures. The frequency of sample collection varies depending on the biomarker.

Blood samples were collected at baseline through Year 9 samples in WHI 1993-2005 at WHI clinical centers; samples for the Long Life Study (LLS) were collected in 2012-2013 at participant homes (approximately years 14-20, depending on when the participant enrolled in WHI).

Pre-diagnostic Sample Collection
Yes

Samples were obtained regardless of diagnoses. Health conditions were self-reported.

Post-treatment Sample Collection
Yes

Samples were obtained regardless of diagnoses. Health conditions were self-reported.

Method of Sample Collection
Participants were asked to fast for at least 12 hours before blood draws. In some cases participants were not fasting. Fasting status is indicated in the database.

 
Participants were allowed to take all regular medications except for insulin or oral medication used to control diabetes. Additionally, participants were asked to take no aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) for 48 hours before the visit; however, NSAIDs that are taken regularly may be continued and taken within the 48 hours before the blood draw, consistent with the participant's usual schedule. Participants were told to neither smoke for at least one hour before the blood draw nor perform vigorous physical activity (such as jogging or bicycling) for at least 8 hours before the blood draw.

Age at Sample Collection
Yes
Date of Sample Collection
Yes
Reason for Sample Collection
Clinical trial

(The purpose of the biorepository is to gain insights into women's susceptibility to certain diseases, which treatments are best for which women, and how to individually tailor preventive care)

Method of Sample Storage
All specimens are stored frozen at -80 degrees Celsius at a central repository in Rockville, MD. Specimen processing for ancillary studies (aliquoting, DNA extraction) occurs in a central lab (specimen processing lab.)
Length of Sample Storage
N/A

(Not available)

Pathology
Samples of normal and disease
DNA Isolation
Yes

Buffy coat is stored frozen in the WHI repository and DNA is extracted from the stored buffy coat when it is requested for an ancillary study. An aliquot is made for the testing lab and the remaining sample is returned to the WHI repository.

DNA has been extracted using different methods over time.

~2000-2003: Qiagen Puregene/Bioserve
~2004-2005: Salt-precipitation
~2005-2008: Phenol Chloroform
~2008 - Present: Qiagen/Five Prime

The current "Five Prime" extraction method was developed by FHCRC using Qiagen reagents in a method designed to maximize both the quality and yield of extracted DNA. An AS may receive DNA samples extracted by different methods in the past, as well as freshly extracted DNA. Extraction method is tracked in the WHI specimen database. Please note that the DNA is extracted on an "as needed" basis, so the date of extraction does not correlate with the date of the blood draw. All Long Life Study DNA has already been extracted using the Five Prime method.

DNA concentration is assessed at the time of extraction. DNA concentration was first assessed using spectrophotometry. Starting in August 2007, DNA concentration has been assessed using PicoGreen. Concentration method is tracked in the WHI specimen database.

RNA Isolation
Yes

A PAXgene tube was collected during the Long Life Study visit. RNA/miRNA was extracted from the PAXgene tube within ~1 month of collection. The concentration of RNA was determined by NanoDrop. The extracted RNA is stored frozen in the WHI repository.

Cell Culture
No
Genetic Testing
Yes

Specimen data from many of the WHI Core and Ancillary studies (AS) is available in the WHI Investigator's dataset, the WHI Database, on WHI AS site pages, and/or on dbGaP. Included in the WHI Investigators' Data is a file indicating which participants have genetic data on dbGaP. Genetic and phenotypic data are routinely submitted to dbGaP. Please refer to the dbGaP website for detailed information on what WHI datasets are currently available, instructions on how to access and download data, searchable FAQs, and dbGaP contact information. For genetic data that are not yet available on dbGaP, or for very limited genetic datasets, data may be available from the WHI Clinical Coordinating Center (CCC) as detailed in our policy for accessing WHI genetic data.

GWAS has been performed through many WHI ancillary studies with different platforms and different outcomes/exposures of interest, but GWAS data from about 30,000 WHI participants were imputed into 1,000 Genomes data. The
harmonization/imputation effort involves 6 different GWAS studies: 1000 Genomes Project reference panel (1092 samples; v2.20101123 for GECCO; v3.20101123 for Hip Fracture, SHARE, GARNET, WHIMS+ MOPMAP). The Harmonized and Imputed GWAS data are available at dbGaP (phs000746), but not all directly genotyped data have been submitted.

More details are available at: https://www.whi.org/researchers/data/SitePages/GWAS%20Data%20and%20Blood%20Specimen%20Results.aspx

Access for Research: Specimens
Yes, for clinical and/or epidemiologic research

(Requires permission via data access application)

Access for Research: Genetic Data
Yes

However, this requires permission via data access application

Access for Research: Epidemiologic Data
Yes

However, this requires permission via data access application

Quality Assurance Procedures
Yes

Sample Stability Monitoring: Pooled samples of serum, citrated and EDTA plasma were created close to the start of WHI enrollment to be tested for core analytes and CVD biomarkers alongside participant samples. Results from these samples allow the Lab Working Group to monitor the stability of primary analytes over time.

Blind Duplicates: WHI uses blood samples from women who consented to the screening blood draw, but were not enrolled or randomized into any WHI component. The samples are relabeled to provide blinded duplicate samples that are included in all batches of assays. When preparing budgets, please include the costs for testing the blind duplicates. There is no covariate data associated with these samples.

WHI includes blind duplicates as quality control samples in all sample pulls, as follows:

DNA: Studies requesting DNA samples are required to include quality control samples: 5% of the total number of participant samples (2.5% blind duplicate pairs). For smaller genotyping studies (e.g. candidate genes, limited SNPs), the WHI-CCC will produce a SNP concordance report that assesses the study's (1) correct identification of the blind duplicates, (2) failure to identify blind duplicates, and (3) unexpected duplicates among all samples provided. For larger genotyping studies (e.g. GWAS, sequencing), the PI is to report to the WHI-CCC all duplicates identified. From this list, the WHI-CCC will confirm the correct/incorrect identification of the blind duplicates and any unexpected duplicates.

Plasma, serum, urine, and RBC: WHI includes 10% blind duplicate QA samples (5% pairs) with all blood and urine samples. The correlation coefficient and the average coefficient of variation % is computed based on the test results for these samples and reported to the PI.

Sample Processing Quality Control: The adequacy of serum and plasma aliquoting by the Specimen Processing Lab is evaluated by testing a sub-aliquot from each blind quality control sample for total cholesterol. Similarly, urine samples are tested for sodium. The correlation and average CV% between the members of each blind pair is computed and reviewed by the WHI Lab Working Group.

Family History
Yes

A family history questionnaire was provided at baseline

Medical History
Yes

Data are based on questionnaires

Biobank Linkage
Genetic database
Other

 
Genetic and phenotypic data are routinely submitted to dbGaP. A subset of the WHI Clinical Trial a​nd Observational Study data is also available through BioLINCC. You do not need a WHI collaborator to access these datasets.

Further, the Women’s Health Initiative Clinical Coordinating Center (WHI CCC) developed a Virtual Data Enclave (VDE) to expand access to selected confidential data for those who meet approved criteria. The VDE allows Investigators with an approved manuscript or ancillary study proposal to remotely access and analyze data on a secure server located at the CCC. Access to data in the VDE is based on the requirements of the specific manuscript or ancillary study proposal. Data in the VDE do not include direct identifiers (e.g., name, social security number).

- Participant medical history and medical services use: Includes diagnoses, medication use, medical provider stays, and medical services usage, dates, and costs and location of services obtained from Medicare (CMS) data linkage, the National Death Index and any other data linkage activities that may be approved and conducted in the future.
- Participant residential history: Includes dates of residence along with latitude, longitude, FIPS code, and zip code of residence since being entered into the WHI database. Actual street addresses will not be included. State/country of birth and state/country of residence at various ages may be included upon request. Please note: Because of the confidentiality protections required for Medicare data, projects requiring linkage of address history or geospatial information with Medicare files are not allowed.
- Participant’s responsible Clinical Center history: Includes Clinical Center ID and the dates the Clinical Center was responsible for the participant over time.
- Participant vital statistics: Includes date of birth and date of death.
- Other participant study related information: Includes dates of enrollment/randomization, dates of consent, and dates of participant contact for collection of data and specimens.

Other study-specific data linkages have been performed (e.g., linkage to the Census 2000 data for the AS464 study or to the genetic SHARe database for the Aftrican-American subgroup).

Field Names
Records
Type of Genetic Database
GWAS database

 
** NOTE: Information on this database is publicly available so the database manager has not reviewed this profile.

The Observational Study of the WHI examines the relationship between lifestyle, environmental, medical and molecular risk factors and specific measures of health or disease outcomes. This component involves tracking the medical history and health habits of 93,676 women not participating in the clinical trial. Recruitment for the observational study was completed in 1998 and participants were followed annually for 8 to 12 years.

The original protocol allowed for follow-up until March 2005, after which participants were invited to enroll in the first WHI Extension Study for follow-up through 2010. Participants were invited again to participate in the second WHI Extension Study with continued follow up from 2010 to 2020. The second WHI Extension Study from 2010 to 2020 enrolled 93,500 consenting participants from the first WHI Extension Study. As part of the second Extension, 80+ year old women were asked to consent to an In Person Visit at their homes during which additional blood samples were collected and various measurements were taken (such as blood pressure, height, weight, waist circumference, grip strength, etc.).

Genetic and phenotypic data from WHI sub-studies re routinely submitted to the database of genotypes and phenotypes (dbGaP). Individual-level genetic and phenotype data are available for 64,291 study subjects.

Source of Genetic Data
Clinical trial data

 
[This WHI dbGaP Cohort release of the WHI baseline and follow-up data includes data collected on study forms, outcomes, results from blood analyses, and computed variables for WHI participants who have been selected for specific studies where genotype data will be submitted to dbGaP.

The WHI study ended March 31, 2005, and the closeout date for data collection was April 8, 2005. Participants consenting to join the first WHI Extension Study were followed through September 30, 2010, primarily for outcomes data collection. Those consenting to the second WHI Extension Study continue to be followed for outcomes data collection (through 2020). This data release includes data through the end of the first WHI Extension Study.

The following clinical sub-studies have reported genotype, expression, and other molecular data from the WHI cohort:
phs000386 WHI SHARe
phs000281 GO-ESP WHISP
phs000315 WHI GARNET
phs000503 WHISE
phs000227 PAGE WHI
phs000675 WHIMS+
phs000746 WHI Harmonized and Imputed GWAS]

Specimen Genotyped
Yes

Buffy coat DNA extracted from blood samples

Tissue Form
Other

(DNA is extracted from buffy coat blood. Buffy coats were removed from the spun EDTA and citrate blood collection tubes and placed in 1.8 ml freezer vials.)

Genetic Template
DNA
Gene-Drug Response
Yes

Data on current medications and current supplements (daily nutrient intake from multivitamins and single supplements) are available. These data can be linked by subject ID with genetic data.

Gene-Disease Relationship
Yes

The current release of outcomes data includes centrally verified, locally verified and self-reported outcomes collected through the first WHI Extension Study for clinical trial, observational study, and Calcium and Vitamin D study. The outcomes data sets include all WHI participants, and the first occurrence of outcomes since the beginning of WHI. Outcomes that are adjudicated or laboratory-tested are:

CARDIOVASCULAR:
- MI
- Stroke
- Congestive heart failure
- Angina
- Peripheral artery disease (PAD)
- Carotid artery disease (CAD)
- Coronary revascularization (PTCA/CABG)
- TIA

CANCER:
- Breast cancer
- Endometrial cancer
- Colorectal cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lung
- Lymphoma, Hodgkin's
- Lymphoma, Non-Hodgkin's
- Pancreas
- Other cancers

FRACTURES:
- Hip
- Non-hip fractures

OTHER:
- Pulmonary embolism
- Deep vein thrombosis
- Hysterectomy
- Death from any cause

Outcomes which are self-reported are:
- Cataracts
- Colorectal polyps/adenomas
- Dementia, Alzheimer's
- Diabetes diagnosis, ever
- Fractures (non-hip)
- Gallbladder disease/stones
- Glaucoma
- Kidney/bladder stones
- Macular degeneration
- Osteoarthritis
- Osteoporosis
- Parkinson's disease
- Rheumatoid arthritis
- SLE

Exams/Procedures:
- Barium enema X-ray
- Blood in stool
- Blood pressure
- Bone density scan
- Breast biopsy/aspiration
- Breast exam
- Breast exam, other (MRI/ultrasound)
- Cholesterol
- D&C
- ECG
- Endometrial biopsy
- Eye exam
- Flex sig/colonoscopy
- Hysterectomy
- Mammogram
- PAP smear
- Physical exam
- Rectal exam

Medication/treatments:
- Anxiety pills
- Depression pills/therapy
- Diabetes mellitus requiring therapy
- Diabetes, diet/exercise
- Diabetes, insulin
- Diabetes, pills
- Estrogen pills
- High blood pressure pills
- High cholesterol pills
- Shots for DVT
- Osteoporosis calcium pills
- Osteoporosis non-calcium pills

Gene-Health Outcome Relationship
Yes

Data on hospitalization are captured. These data can be linked by subject ID with genetic data.

Gene-Environment Response
Yes

Data are captured on diet, lifestyle, activities, personal habits (smoking, coffee, alcohol), social/personal support and satisfaction. These data can be linked by subject ID with genetic data.

Method of Imputing Genetic Data
Yes

GWAS has been performed through many WHI ancillary studies with different platforms and different outcomes/exposures of interest, but GWAS data from about 30,000 WHI participants were imputed into 1,000 Genomes data. The harmonization/imputation effort involves 6 different GWAS studies: The 1000 Genomes Project reference panel (1092 samples; v2.20101123 for GECCO; v3.20101123 for Hip Fracture, SHARE, GARNET, WHIMS+ MOPMAP).
The Harmonized and Imputed GWAS data are available at dbGaP (phs000746), but not all directly genotyped data have been submitted.

Genetic Variant Identification
Other

[The full genetic dataset (restricted access) includes dbSNP accession / rsID). The publicly available dbGaP records include the following gene identifiers form WHI:
- Gap accession number,
- BioSample number, and
- Sequence Read Archive (SRA).]

Genetic Data Level
Individual
Aggregate - by study population
Genotyping Method
Yes

Both, the genotyping method (PCR, Illumina array, Affymatrix array) and genotype data (SNP or whole exome) are indicated

Method of Genetic Variant Filtering
N/A

(Not available)

Haplotypes
Yes

(in SHARe study)

Haplogroups
No
Variable Number of Tandem Repeats (VNTR)
No

However, may obtain via linkage to dbSNP database

Single Nucleotide Polymorphisms (SNPs)
Yes

Linked to the dbSNP database available as SNP accession / rsID

Variant Type
SNPs
Variant Class
No
Mutation Indicated
No
Position
Yes
Amino Acid Change
No
Genotype / Polymorphism
Yes

Also available via linkage to dbSNP database

Allele Frequency
Yes

Nucleotide substitution (e.g., C/T)

Linkage Disequilibrium (r²)
Yes
Noncarriers Indicated
Yes
Association Statistics
No

The database does not report association statistics, but individual GWAS studies included statistical analyses, often reporting the odds ratio with respect to phenotype(s) of interest.

Genetic Relatedness Pairing
Yes

Varied from study to study; for example, in SHARe, genetic relatedness among subjects within the same ethnicity was examined using pair-wise identity-by-descent (IBD) estimation

Data Sharing: Genetic Data
Yes, access to genetic data is available - for epidemiologic research only

 
WHI participants have been included in multiple genome-wide, sequencing, exome-wide, and other genotyping efforts. The distribution of WHI genetic data has historically been handled through a 3rd party (dbGaP). To promote collaborative research with existing WHI principal investigators, and at the request of the NHLBI project office, WHI has added a direct means to access WHI genetic data. Access to genetic data is limited to WHI Principal Investigators, pending approval.

Space needed for the whole set of compressed imputed GWAS data is 2 terabytes. Data are broken into files by study and chromosome, but generally not further (smaller subsets of SNPs will not be extracted for Investigators). Data must be downloaded within 7 days, and can only be downloaded one time using the link (for security purposes) in the e-mail sent by WHI staff.

Access for Research
No, access to specimen/genetic data is not allowed

The users must agree not to distribute data obtained to any entity or individual not covered in the data access request.

Genetic Data Linkage
N/A

(Not applicable)

Description of Genetic Data Linkage
Genetic and phenotypic data are routinely submitted to dbGaP. A subset of the WHI Clinical Trial and Observational Study data is also available through BioLINCC. You do not need a WHI collaborator to access these datasets.

In 2010, the WHI SNP Health Association Resource (SHARe) dataset was released on dbGaP. The dataset includes extensive phenotypic and genotypic data on 12,008 African American and Hispanic women aged 50-79 enrolled in one or more components of the WHI program.
Field Names
Records
Cost Data
No
Cost Denomination
N/A

(Not applicable)

Type of Cost Data
N/A

(Not applicable)

Description of Surrogate Link
N/A

(Not applicable)

Field Names
Records
Data Validation Against Original Source
Yes

 
For WHI clinical outcomes of interest, data were ascertained by self-report on the routine Form 33 - Medical History Update - administered semi-annually to Clinical Trial participants and annually to Observational Study participants. Those participants who reported a potential WHI-defined outcome were then contacted by mail or phone and a Form 33D – Medical History Update (Detail) was completed to obtain more specific information on newly diagnosed health conditions or recent procedures. Investigation of potential WHI clinical outcomes depended on the type of outcome, the participant’s study component, and whether or not the outcome was a first versus a recurrent event. A documentation set was defined for each type of WHI clinical outcome, and these medical records were used for adjudication.

Local Adjudication - Based on specific adjudication criteria, a physician adjudicator at the local Clinical Center either confirmed or denied a potential clinical outcome. Data on confirmed WHI outcomes were entered on outcomes-specific forms for cardiovascular disease, cancer, fracture, hysterectomy, venous thromboembolic disease, as well as hospitalizations and deaths.

Central Adjudication - WHI Clinical Centers were asked to send selected locally adjudicated case packets to the Clinical Coordinating Center for central adjudication, depending on the type of outcome and the participant’s study component. Centrally-trained cardiovascular physician adjudicators (and neurologists, in the case of stroke outcomes) reviewed and adjudicated cardiovascular and death outcomes. The five primary cancers (breast, colon, rectum, endometrium, and ovary) were coded centrally by tumor registry coders. All hip fractures were centrally adjudicated at the WHI Bone Density Center.

Access to Medical Records
No
Linkage to Other Databases
Yes
Brief Description of Linkage Capabilities

The WHI Central Coordinating Center (CCC) developed a Virtual Data Enclave (VDE) to expand access to selected confidential data for those who meet approved criteria. The VDE allows Investigators with an approved manuscript or ancillary study proposal to remotely access and analyze data on a secure server located at the CCC. Access to data in the VDE is based on the requirements of the specific manuscript or ancillary study proposal. Data in the VDE do not include direct identifiers (e.g., name, social security number).

- Participant medical history and medical services use: Includes diagnoses, medication use, medical provider stays, and medical services usage, dates, and costs and location of services obtained from Medicare (CMS) data linkage, the National Death Index and any other data linkage activities that may be approved and conducted in the future.
- Participant residential history: Includes dates of residence along with latitude, longitude, FIPS code, and zip code of residence since being entered into the WHI database. Actual street addresses will not be included. State/country of birth and state/country of residence at various ages may be included upon request.
Please note: Due to confidentiality protections required for Medicare data, projects requiring linkage of address history or geospatial information with Medicare files are not allowed.
- Participant’s responsible Clinical Center history: Includes Clinical Center ID and the dates the Clinical Center was responsible for the participant over time.
- Participant vital statistics: Includes date of birth and date of death.
- Other participant study related information: Includes dates of enrollment/randomization, dates of consent, and dates of participant contact for collection of data and specimens.

Genetic and phenotypic data are routinely submitted to dbGaP.  A subset of the WHI Clinical Trial and Observational Study data is also available through BioLINCC. You do not need a WHI collaborator to access these datasets.

 
In 2010, the Women’s Health Initiative (WHI) SNP Health Association Resource (SHARe) dataset was released on dBGaP. The dataset includes extensive phenotypic and genotypic data on 12,008 African American and Hispanic women aged 50-79 enrolled in one or more components of the WHI program.

Other study-specific data linkages have been performed (e.g., linkage to the Census 2000 data for the AS464 study).

Field Names
Records
Database Contact Data

Women's Health Initiative Program Office
2 Rockledge Centre
Suite 10018, MS 7936
6701 Rockledge Drive
Bethesda, MD 20892-7936 (U.S. Postal Service)
Bethesda, MD 20817-7936 (Express Mail Service)
USA
Phone: (301) 402-2900
Fax: (301) 480-5158
E-mail: nm9o@nih.gov

** NOTE: In contrast to our usual policy, this profile has not been reviewed by the DBM. We are continuing to seek further information on the fields with missing data.

Alternate Contact

N/A

(Not applicable)

Source of Database Funding
Government
Private

(WHI is sponsored by the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI). The Fred Hutchinson Cancer Research Center in Seattle, WA served as the WHI Clinical Coordinating Center for data collection, management, and analysis. The WHI CPS component was a 5-year cooperative venture with the Centers of Disease and Prevention (CDC).)

Sponsoring Government Agency
National Institutes of Health (NIH) - National Heart, Lung, and Blood Institute (NHLBI)
Sponsoring Pharmaceutical Manufacturer

N/A

(Not applicable)

Database Usage Restrictions
Public & Private Access

Access to WHI Datasets is governed by study policy. The current policy requires that in order to gain access to WHI Datasets, you must belong to one of the following categories:
- Current WHI Principal Investigator
- Ancillary Study Principal Investigator
- Former Principal Investigator who was active during the first WHI Extension (2005-2010) for at least one year
- Lead author on an approved paper
Individuals meeting the above criteria who wish to gain access to WHI Datasets must return a signed copy of the WHI Data Distribution Agreement to the WHI CCC.

Questions regarding gaining access to or downloading datasets can be addressed to the WHI Helpdesk (helpdesk@whi.org)

De-identified genotyping data (https://cleo.whi.org/data/Pages/GWAS-Data.aspx) can be requested at the The Biologic Specimen and Data Repository Coordinating Center (BioLINCC) website. Researchers wishing to collaborate with an WHI investigator or interested in applying for future Broad Agency Announcement (BAA) funding must visit the WHI Scientific Resources website (https://cleo.whi.org/researchers/SitePages/Propose%20a%20Study.aspx)

Charge for Database Usage
No
Data Media Format
PDF Files
Other

[Aggregate data are availabe as PDFs at https://cleo.whi.org/data/SitePages/Baseline%20Summary%20Tables.aspx (Baseline Summary Tables), and at https://cleo.whi.org/data/SitePages/Outcomes%20Summary%20Tables.aspx (Outcome Summary Tables).]

Number of Publications Using Database
~2000
References of Studies Using/Describing Database

1. Crawford L, Reeves KW, Luisi N, Balasubramanian R, Sturgeon SR. Perineal powder use and risk of endometrial cancer in postmenopausal women. Cancer Causes Control. 2012 Oct;23(10):1673-80.

2. Hartz A, He T, Ross JJ. Risk factors for colon cancer in 150,912 postmenopausal women. Cancer Causes Control. 2012 Oct;23(10):1599-605.

3. Chen BH, Brennan K, Goto A, Song Y, Aziz N, You NC, Wellons MF, Manson JE, White DL, Butch AW, Liu S. Sex hormone-binding globulin and risk of clinical diabetes in american black, Hispanic, and asian/pacific islander postmenopausal women. Clin Chem. 2012 Oct;58(10):1457-66.

4. Wang L, Manson JE, Gaziano JM, Liu S, Cochrane B, Cook NR, Ridker PM, Rifai N, Sesso HD. Plasma adiponectin and the risk of hypertension in white and black postmenopausal women. Clin Chem. 2012 Oct;58(10):1438-45.

5. Lemogne C, Consoli SM, Panjo H, Nabi H, Goldberg M, Zins M, Ringa V. Personality and hormone therapy use among postmenopausal women in the GAZEL cohort study. Fertil Steril. 2012 Oct;98(4):929-936.

6. Buhling KJ, von Studnitz FS, Jantke A, Eulenburg C, Mueck AO. Use of hormone therapy by female gynecologists and female partners of male gynecologists in Germany 8 years after the Women's Health Initiative study: results of a survey. Menopause. 2012 Oct;19(10):1088-91.

7. Karsdal MA, Bay-Jensen AC, Henriksen K, Christiansen C. The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation: may estrogen be a magic bullet? Menopause Int. 2012 Sep 28. [Epub ahead of print] PubMed PMID:23024184.

8. Orchard TS, Ing SW, Lu B, Belury MA, Johnson K, Wactawski-Wende J, Jackson RD. The association of red blood cell n-3 and n-6 fatty acids to dietary fatty acid intake, bone mineral density and hip fracture risk in the Women's Health Initiative. J Bone Miner Res. 2012 Sep 27. doi: 10.1002/jbmr.1772. [Epub ahead of print] PubMed PMID: 23018646.

9. Rossouw JE, Prentice RL, Manson JE, Aragaki AK, Hsia J, Martin LW, Kuller L, Johnson KC, Eaton C, Jackson R, Trevisan M, Allison M, Hoogeveen RC. Relationships of coronary heart disease with 27-hydroxycholesterol, low-density lipoprotein cholesterol, and menopausal hormone therapy. Circulation. 2012 Sep 25;126(13):1577-86.

10. Simon MS, Chlebowski RT, Wactawski-Wende J, Johnson KC, Muskovitz A, Kato I, Young A, Hubbell FA, Prentice RL. Estrogen Plus Progestin and Colorectal Cancer Incidence and Mortality. J Clin Oncol. 2012 Sep 24. [Epub ahead of print] PubMed PMID: 23008295.

Database Contact
Database Contact Data

Women's Health Initiative Program Office
2 Rockledge Centre
Suite 10018, MS 7936
6701 Rockledge Drive
Bethesda, MD 20892-7936 (U.S. Postal Service)
Bethesda, MD 20817-7936 (Express Mail Service)
USA
Phone: (301) 402-2900
Fax: (301) 480-5158
E-mail: nm9o@nih.gov

Alternate Contact

N/A

References of Studies Using/Describing Database

1. Crawford L, Reeves KW, Luisi N, Balasubramanian R, Sturgeon SR. Perineal powder use and risk of endometrial cancer in postmenopausal women. Cancer Causes Control. 2012 Oct;23(10):1673-80.

2. Hartz A, He T, Ross JJ. Risk factors for colon cancer in 150,912 postmenopausal women. Cancer Causes Control. 2012 Oct;23(10):1599-605.

3. Chen BH, Brennan K, Goto A, Song Y, Aziz N, You NC, Wellons MF, Manson JE, White DL, Butch AW, Liu S. Sex hormone-binding globulin and risk of clinical diabetes in american black, Hispanic, and asian/pacific islander postmenopausal women. Clin Chem. 2012 Oct;58(10):1457-66.

4. Wang L, Manson JE, Gaziano JM, Liu S, Cochrane B, Cook NR, Ridker PM, Rifai N, Sesso HD. Plasma adiponectin and the risk of hypertension in white and black postmenopausal women. Clin Chem. 2012 Oct;58(10):1438-45.

5. Lemogne C, Consoli SM, Panjo H, Nabi H, Goldberg M, Zins M, Ringa V. Personality and hormone therapy use among postmenopausal women in the GAZEL cohort study. Fertil Steril. 2012 Oct;98(4):929-936.

6. Buhling KJ, von Studnitz FS, Jantke A, Eulenburg C, Mueck AO. Use of hormone therapy by female gynecologists and female partners of male gynecologists in Germany 8 years after the Women's Health Initiative study: results of a survey. Menopause. 2012 Oct;19(10):1088-91.

7. Karsdal MA, Bay-Jensen AC, Henriksen K, Christiansen C. The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation: may estrogen be a magic bullet? Menopause Int. 2012 Sep 28. [Epub ahead of print] PubMed PMID:23024184.

8. Orchard TS, Ing SW, Lu B, Belury MA, Johnson K, Wactawski-Wende J, Jackson RD. The association of red blood cell n-3 and n-6 fatty acids to dietary fatty acid intake, bone mineral density and hip fracture risk in the Women's Health Initiative. J Bone Miner Res. 2012 Sep 27. doi: 10.1002/jbmr.1772. [Epub ahead of print] PubMed PMID: 23018646.

9. Rossouw JE, Prentice RL, Manson JE, Aragaki AK, Hsia J, Martin LW, Kuller L, Johnson KC, Eaton C, Jackson R, Trevisan M, Allison M, Hoogeveen RC. Relationships of coronary heart disease with 27-hydroxycholesterol, low-density lipoprotein cholesterol, and menopausal hormone therapy. Circulation. 2012 Sep 25;126(13):1577-86.

10. Simon MS, Chlebowski RT, Wactawski-Wende J, Johnson KC, Muskovitz A, Kato I, Young A, Hubbell FA, Prentice RL. Estrogen Plus Progestin and Colorectal Cancer Incidence and Mortality. J Clin Oncol. 2012 Sep 24. [Epub ahead of print] PubMed PMID: 23008295.