W66 - Long Life Study-Phase III Biomarkers and GWAS

Investigator Names and Contact Information

Introduction/Intent

The original Long Life Study (W64) eligible population (Phase I) consisted of 9,930 women who were at least 72 years old. In May 2012, it was clear that the consent rate was much lower than anticipated, and the decision was made to add 2651 younger women (Phase II) to the pool of eligibles. All of the women eligible for Phases I and II had samples sent for baseline biomarkers (lipids, CRP, Creatinine, Glucose, and Insulin) from either SHARe Biomarkers (W54) or EA HT Biomarkers (W58) and GWAS data from either SHARe (M5), GARNET (M13), or ‘WHIMS+’ (W63).

In July 2012, it was determined that the Long Life Study’s consent rate would not likely exceed 65% and that the participation rate among all eligible would not likely exceed 88%. As a result, a decision was made to add another 1500 eligible women (Phase III). As all MRC participants who met the Phase I and II baseline biomarker/GWAS requirement were included in Phases I and II, the Phase III participants would not have this key set biomarkers/GWAS data available.

The objective of this proposal is to obtain baseline biomarkers and GWAS data on the 1500 women in the Long Life Study’s Phase III.

Methods

The biomarkers (triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, glucose, insulin, creatinine, and CRP) will be measured using the same laboratory (University of Minnesota Medical Center) and laboratory methods​ as were used for W54​ and W58​. Following quality control checks and Laboratory Working Group review, the biomarker data for these women has been incorporated into the WHI Investigators’ Dataset.

The GWAS data will be generated from the same laboratory (The Broad Institute) and platform (Illumina Omni-Express/Exome) as were used for W63​. The laboratory has provided called genotypes to the WHI CCC. Following data cleaning and quality checks, the genetic data for these women will be added to dbGaP (date TBD).

Related Papers

Genomic predictors of venous thromboembolism

Approved Proposal, Smith, Nicholas et al., 2016/12 MSID: 3227
Keywords: Venous Thrombosis; Venous Thromboembolism; Genetics; Genome-Wide Association Study; Meta-Analysis
Related Studies: 264, M5, M13, W63, W66

Insulin level and risk of non-Hodgkin lymphoma among postmenopausal women in The Women’s Health Initiative

Approved Proposal, Peila, Rita et al., 2016/11 MSID: 3202
Keywords: Insulin; Type 2 Diabetes; Inflammation; C-Reactive Protein; Non-Hodgkin Lymphoma

Adiposity, history of diabetes, and risk of pancreatic cancer in postmenopausal women

Rhonda Arthur et al., 2018/9 PubMed #30449532 MSID: 3447
PURPOSE: The purpose of this study was to examine the association of type II diabetes and anthropometric variables with risk of pancreatic cancer among postmenopausal women. METHODS: Weight, height, waist circumference, and hip circumference were measured by trained personnel, whereas history of diabetes and weight earlier in life were self-reported. Pancreatic cancer was ascertained via central review of medical records by physician adjudicators. After exclusions, 1045 cases of pancreatic cance...
Keywords: Adiposity; Body Mass Index; Waist Circumference; Waist-Hip Ratio; Serum Insulin; Pancreatic Cancer; Postmenopausal Women
Related Studies: W54, W58, W66

Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Valerie Turcot et al., 2018/1 PubMed #29273807 MSID: 3337
Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (Z...
Related Studies: 224, BA14, BA18, M13, W63, W66

A large-scale exome array analysis of venous thromboembolism

Sara Lindstrom et al., 2019/1 PubMed #30659681 MSID: 3296
Although recent Genome-Wide Association Studies have identified novel associations for common variants, there has been no comprehensive exome-wide search for low-frequency variants that affect the risk of venous thromboembolism (VTE). We conducted a meta-analysis of 11 studies comprising 8,332 cases and 16,087 controls of European ancestry and 382 cases and 1,476 controls of African American ancestry genotyped with the Illumina HumanExome BeadChip. We used the seqMeta package in R to conduct sin...
Keywords: Venous Thrombosis; Venous Thromboembolism; Genetics; Exome Array; Meta-Analysis
Related Studies: 224, M13, M24, W63, W66

QT/JT/QRS GWAS meta-analysis – CHARGE EKG Collaboration

Approved Proposal, Young, William et al., 2018/8 MSID: 3670
Keywords: Gwas; Qt Interval; Jt Interval; Qrs Interval; Ecgs
Related Studies: 224, 264, BA3, M5, W63, W66

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Mengzhen Liu et al., 2019/1 PubMed #30643251 MSID: 3580
Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phe...
Related Studies: 224, 264, BA3, M13, W63, W66

Analysis of pleiotropic genetic effects on cognitive impairment, systemic inflammation and plasma lipids in the WHIMS study

Approved Proposal, Hayden, Kathleen et al., 2018/3 MSID: 3587
Keywords: Genetic Pleiotropy; Cognitive Decline; Mild Cognitive Impairment; Dementia; Alzheimer’S Disease
Related Studies: 349, M5, M13, W63, W66

Electrocardiographic p-wave duration reveals diverse genetic mechanisms of atrial fibrillation

Approved Manuscript, Weng, Lu-Chen et al., 2019/10 MSID: 3994
Keywords: Electrocardiology (Ecg); Genetics; Association Studies; Atrial Fibrillation
Related Studies: 224, 264, BA3, M5, W63, W66

Broad clinical manifestations of polygenic risk for coronary artery disease in the Women’s Health Initiative

Shoa Clarke et al., 2022/8 PubMed #36034645 MSID: 3914
Background: The genetic basis for coronary artery disease (CAD) risk is highly complex. Genome-wide polygenic risk scores (PRS) can help to quantify that risk, but the broader impacts of polygenic risk for CAD are not well characterized. Methods: We measured polygenic risk for CAD using the meta genomic risk score, a previously validated genome-wide PRS, in a subset of genotyped participants from the Women's Health Initiative and applied a phenome-wide association study framework to assess assoc...
Keywords: Polygenic Risk Score; Genetic Risk Score; Phenome-Wide Association Study; Coronary Artery Disease; Cardiovascular Disease; Myocardial Infarction; Coronary Revascularization
Related Studies: 224, 264, 349, 564, BA3, M5, M13, M18, W63, W66

Dietary Inflammatory Potential and the Risk of Incident Kidney Failure in the Women’s Health Initiative

Tanya Johns et al., 2025/4 PubMed #40789098 MSID: 3842
Background: Diet affects inflammation and kidney health, but few studies have investigated dietary inflammatory potential in CKD progression, particularly in women. We aim to examine this association in the Women's Health Initiative (WHI). Methods: We conducted a non-concurrent prospective cohort study among WHI participants enrolled in the clinical trials and observational study (1993-1998) without baseline CKD and with available dietary intake assessments, Medicare data, and creatinine measure...
Keywords: Diet; Inflammation; End-Stage Renal Disease; Chronic Kidney Disease; Racial Disparities; Aging
Related Studies: 422, W35, W54, W58, W66

Metabolic obesity phenotype, age acceleration and obesity-related cancer risk in the Women’s Health Initiative

Approved Proposal, Karra, Prasoona et al., 2023/3 MSID: 4878
Keywords: Obesity-Associated Cancer; Metabolic Dysfunction; Body Mass Index; Metabolic Health Phenotypes; Age Acceleration
Related Studies: 311, 315, 564, BA23, W1, W2, W54, W58, W66

Leukocyte telomere dynamics: associations with cardiovascular aging and survival in the WHI Long Life Study

Approved Proposal, Aviv, Abraham et al., 2015/5 MSID: 2677
Keywords: Telomere Length; Telomere Attrition; Aging; Cardiovascular Disease; Mortality; Cardiovascular Disease Risk Factors
Related Studies: BA25, W64, W66

Premenopausal Endogenous Estrogen Exposure and Kidney Function in Postmenopausal Women: The Women's Health Initiative

Approved Proposal, Lapierre-Nguyen, Stephanie et al., 2025/8 MSID: 5381
Keywords: Estrogen Exposure; Chronic Kidney Disease; Premenopausal Exposures; Kidney Function
Related Studies: 422, 717, W35, W54, W58, W66

Allostatic load and risk of acute infection and post-acute sequelae of SARS-CoV-2 in the Women’s Health Initiative

Approved Proposal, Cirovic, Christine et al., 2025/1 MSID: 5217
Keywords: Long Covid; Pasc; Allostatic Load; Social Determinants Of Health (Sdoh)
Related Studies: W6, W66

Kidney stones and the risk of chronic kidney disease among postmenopausal women: Results from The Women's Health Initiative

Approved Proposal, Javadi, Mahsa et al., 2024/2 MSID: 5020
Keywords: Urinary Tract Stones; Chronic Kidney Disease; End-Stage Kidney Disease (Eskd); Mortality; Hazard Ratio; Postmenopausal Women
Related Studies: 422, M5, M13, W54, W58, W64, W66