AS311 - Global DNA methylation measured in prospectively collected blood samples and risk of bladder cancer among post-menopausal women

Investigator Names and Contact Information

Parveen Bhatti (pbhatti@fredhutch.org)

Introduction/Intent

Specific Aims Primary aim:

  1. To identify specific loci of DNA methylation (CpG loci), in pre-diagnostic specimens, whose methylation profiles are associated with risk of PTCC BC. Risk factors for BC will be controlled for in these analyses.

Secondary aims:

  1. To evaluate if known and suspected bladder cancer risk factors, including smoking, air pollution, reproductive factors, dietary factors and germline genetic variants identified through genome-wide association studies act through an effect on DNA methylation. We will focus on the potential mediating effects of the CpG loci identified through our primary aim, but for the analysis of germline genetic variants we will also examine CpG loci that are proximal to these variants.

  2. To construct BC prediction models with loci-specific methylation variables identified in the primary aim and to add known BC risk factors, including previously identified germline genetic variants.

Data Dictionaries and Study Documentation

This section displays all study-related data dictionaries and study-related files. The investigators for this study will upload the datasets, data dictionaries, and other study-related files. Study-related files will be made available to the public one year after the completion of the ancillary study, with the exception of the datasets, which will only be available to those with a Data Distribution Agreement. Those will be available to those with permission to download and will appear as a download link next to the data dictionary

Data Dictionaries

Name
Description
No results found

Study Documents

Name
Description
Nameanc311 _memo_ September2013.docDescription

Related Papers

Dietary patterns and biological aging in the Women’s Health Initiative

Approved Proposal, Reynolds, Lindsay et al., MSID: 5060
Keywords: Diet Quality; Dna Methylation; Epigenetic Aging; Frailty; Biological Aging
Related Studies: 311, 315, BA23

Dietary patterns and epigenetic aging in the Women’s Health Initiative

Lindsay Reynolds et al., 2024/1 PubMed #38215906 MSID: 4491
Background: Higher diet quality scores are associated with a lower risk for many chronic diseases and all-cause mortality; however, it is unclear if diet quality is associated with aging biology. Objective: This study aimed to examine the association between diet quality and a measure of biological aging - epigenetic aging. Design: A cross-sectional data analysis was used to examine the association between three diet quality scores based on self-reported food frequency questionnaire (FFQ) data a...
Keywords: Mediterranean Diet; Dna Methylation; Epigenetic Aging; Physical Function; Biological Aging
Related Studies: 311, 315, BA23

Epigenome-wide association study (EWAS) of exceptional aging in the Women’s Health Initiative

Approved Proposal, Jain, Purva et al., 2020/5 MSID: 4182
Keywords: Epigenetic; Aging; Cognitive Function; Intact Mobility; Longevity
Related Studies: 39, 311, 315, BA23

Association of clonal hematopoiesis and mosaic chromosomal alterations with solid malignancy incidence and mortality

Pinkal Desai et al., 2024/11 PubMed #39012906 MSID: 3648
Background: Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways. Methods: The authors analyzed whole genome sequencing data from the Trans-Omics for Precision Medicine Women's Health Initiative study (n = 10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal can...
Keywords: Clonal Hematopoesis; Cancer; Cancer Specific Mortality; Breast Cancer; Colorectal Cancer; Lung Cancer; Hematologic Malignancies
Related Studies: 311, 315, 564, BA23

Impact of childhood secondhand smoking exposure on later health outcomes through DNA methylation

Approved Proposal, Jhun, Min A. et al., 2020/6 MSID: 4223
Keywords: Childhood Secondhand Smoking; Dna Methylation; Race/Ethnic Differences; Epigenetics; Health Disparity
Related Studies: 311, 315, BA23

An analysis of clonal hematopoiesis and adiposity measures in the Women’s Health Initiative TOPMED cohort

Approved Proposal, Desai, Pinkal et al., 2020/7 MSID: 4246
Keywords: Clonal Hematopoiesis; Chip; Obesity; Adiposity
Related Studies: 311, 315, 628, BA23

Epigenome-wide association study of diet quality in Women’s Health Initiative and TwinsUK cohort

Publication, Leet, Whitney et al., 2019/10 MSID: 3676
Keywords: Diet; Epigenetics; Insulin Resistance; Type 2 Diabetes
Related Studies: 311, 315, 534, BA23

Early life exposure impacts on racial/ethnic and socioeconomic differences in DNA methylation

Approved Proposal, Jhun, Min A. et al., 2020/2 MSID: 4108
Keywords: Early Life; Dna Methylation; Race/Ethnic Differences; Epigenetics; Health Disparity
Related Studies: 311, 315, BA23

Leukocyte traits and exposure to ambient particulate matter air pollution in the Women’s Health Initiative and Atherosclerosis Risk in Communities study

Rahul Gondalia et al., 2020/1 PubMed #31903802 MSID: 3251
BACKGROUND: Inflammatory effects of ambient particulate matter (PM) air pollution exposures may underlie PM-related increases in cardiovascular disease risk and mortality, although evidence of PM-associated leukocytosis is inconsistent and largely based on small, cross-sectional, and/or unrepresentative study populations. OBJECTIVES: Our objective was to estimate PM-leukocyte associations among U.S. women and men in the Women's Health Initiative and Atherosclerosis Risk in Communities study (n=1...
Keywords: Air Pollution; Particulate Matter; Leukocytes
Related Studies: 311, 315, BA23

Association between epigenetic age acceleration and postmenopausal estradiol in the Women’s Health Initiative

Approved Manuscript, Binder, Alexandra M. et al., 2021/8 MSID: 3725
Keywords: Aging; Postmenopausal Health; Estradiol; Epigenetics; Epigenetic Clock; Breast Cancer
Related Studies: 311, 315, 584, BA23

Integration of epigenetic age acceleration into postmenopausal breast cancer risk prediction models in the Women’s Health Initiative

Approved Proposal, Binder, Alexandra M. et al., 2018/12 MSID: 3726
Keywords: Aging; Postmenopausal Health; Estradiol; Epigenetics; Epigenetic Clock; Breast Cancer
Related Studies: 311, 315, 584, BA23

Replication of a methylome-wide association study of socioeconomic adversity and obesity

Approved Proposal, Fernández-Rhodes, Lindsay et al., 2019/12 MSID: 4050
Keywords: Socioeconomic Position; Obesity; Methylation; Epigenetics
Related Studies: 311, 315, BA23

Response to a request to contribute to a methylome-wide association study of ambient particulate matter air pollution and roadway proximity

Approved Proposal, Collins, Jason et al., 2020/4 MSID: 4149
Keywords: Dna; Methylation; Particulate Matter; Ewas; Roadways
Related Studies: 311, 315, BA23

History of alcohol use and genome-wide methylation in the Women’s Health Initiative Study

Approved Proposal, Bhatti, Parveen et al., 2016/3 MSID: 3023
Keywords: Alcohol; Epigenetics; Dna Methylation; Age Acceleration; Carcinogenesis
Related Studies: 311, 315, BA23

Stressful life events, social support, and epigenetic aging in the Women’s Health Initiative

Harlyn Skinner et al., 2023/12 PubMed #38149693 MSID: 4386
Background: Elevated psychosocial stress has been linked with accelerated biological aging, including composite DNA methylation (DNAm) markers that predict aging-related outcomes ("epigenetic age"). However, no study has examined whether stressful life events (SLEs) are associated with epigenetic age acceleration in postmenopausal women, an aging population characterized by increased stress burden and disease risk. Methods: We leveraged the Women's Health Initiative, a large muti-ancestry cohort...
Keywords: Stressful Life Events; Psychosocial Stress; Dna Methylation; Epigenetic Age Acceleration; Social Support
Related Studies: 311, 315, BA23

Estrogen exposure, DNA methylation and breast cancer risk

Approved Proposal, Palma Gudiel, Helena et al., 2020/1 MSID: 4094
Keywords: Dna Methylation; Stressful Life Events; Social Support; Cardiovascular Disease; Coronary Heart Disease; Stroke
Related Studies: 311, 315, BA23

Epigenomic signatures of circulating polyunsaturated fatty acids in humans: a meta-analysis of 7 studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium

Approved Manuscript, Tintle, Nathan et al., 2020/11 MSID: 3234
Keywords: Linoleic Acid; Epa; Dha; Ala; Methylation; Fatty Acids
Related Studies: 311, 315, BA19, BA23

Epigenetically mediated electrocardiographic manifestations of sub-chronic exposures to ambient particulate matter air pollution in the Women's Health Initiative and Atherosclerosis Risk in Communities Study

Rahul Gondalia et al., 2021/4 PubMed #33895111 MSID: 3361
Background: Short-duration exposure to ambient particulate matter (PM) air pollution is associated with cardiac autonomic dysfunction and prolonged ventricular repolarization. However, associations with sub-chronic exposures to coarser particulates are relatively poorly characterized as are molecular mechanisms underlying their potential relationships with cardiovascular disease. Materials and methods: We estimated associations between monthly mean concentrations of PM < 10 µm and 2.5-10 µm in d...
Keywords: Air Pollution; Dna Methylation; Particulate Matter; Mediation; Heart Rate Variability
Related Studies: 311, 315, BA23

Differential DNA methylation in blood as a mediator of the association between cigarette smoking and bladder cancer risk among postmenopausal women

Kristina Jordahl et al., 2019/6 PubMed #31232174 MSID: 3559
Smoking accounts for approximately 52% of bladder cancer incidence among postmenopausal women, but the underlying mechanism is poorly understood. Our study investigates whether changes in DNA methylation, as measured in blood, mediate the impact of smoking on bladder cancer risk among postmenopausal women. We conducted analyses among 206 cases and 251 controls that were current or never smokers at baseline from a previous case-control study of bladder cancer and genome-wide DNA methylation neste...
Keywords: Dna Methylation; Bladder Cancer; Smoking; Mediation; Epigenetics
Related Studies: 311

Pharmacoepigenomics: human population studies of DNA methylation and statin treatment response

Approved Proposal, Floyd, James et al., 2017/5 MSID: 3381
Keywords: Dna Methylation; Ldl Cholesterol; Statin; Drug-Gene Interaction; Ewas
Related Studies: 311, 315, 534, BA23

Aircraft noise and DNA methylation

Approved Proposal, Holliday, Katie et al., 2017/4 MSID: 3339
Keywords: Epigenetics; Aircraft; Noise; Epigenome-Wide Association Study; Dna Methylation
Related Studies: 311, 315, 534, BA5, BA16, BA23

Epigenetic analyses of age at menopause and phenotypes related to estrogen exposure

Approved Proposal, Leet, Whitney et al., 2021/9 MSID: 4562
Keywords: Dna Methylation; Menopause; Reproductive Years; Epigenetics; Late Menopause
Related Studies: 311, 315, BA23

Postmenopausal hormone therapy and DNA methylation levels in blood

Approved Proposal, Kusters, Cynthia D. et al., 2017/10 MSID: 3420
Keywords: Postmenopausal Hormone Therapy; Dna Methylation; Reproductive Characteristics; Epigenetics; Estrogen Risk Scores
Related Studies: 311, 315, BA23

Psychosocial stress, DNA methylation and incident cardiovascular disease

Approved Proposal, Zannas, Anthony et al., 2020/6 MSID: 4090
Keywords: Dna Methylation; Stressful Life Events; Social Support; Cardiovascular Disease; Coronary Heart Disease; Stroke
Related Studies: 311, 315, BA23

Systems Age: A single blood methylation test to quantify aging heterogeneity across 11 physiological systems

Approved Manuscript, Levine, Morgan et al., 2022/10 MSID: 4601
Keywords: Dna Methylation; Aging; Morbidity; Mortality; Biomarkers
Related Studies: 311, 315, BA23

Epigenetic signatures for breast cancer underlying glucose intolerance in minority subpopulations

Approved Proposal, Jung, Su Yon et al., 2024/10 MSID: 5092
Keywords: Cancer; Breast Carcinogenesis; Glucose Intolerance; Dna Methylation; Minority Subpopulations
Related Studies: 311, 315, 564, BA23

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

Analysis of epigenetic age acceleration and healthy longevity among older US women

Purva Jain et al., 2022/7 PubMed #35895062 MSID: 4181
Importance: Accelerated biological aging is associated with decreased physical capability and cognitive functioning, which are associated with increased risk of morbidity and mortality. Objective: We investigated associations between epigenetic age acceleration (EAA), a biomarker associated with aging, and healthy longevity among older women. Design, setting, and participants: This cohort study was a secondary analysis of participants in the Women's Health Initiative (WHI) who were eligible to s...
Keywords: Epigenetic; Aging; Cognitive Function; Intact Mobility; Longevity
Related Studies: 39, 311, 315, BA23

Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation

Rahul Gondalia et al., 2019/6 PubMed #31208937 MSID: 3188
BACKGROUND: DNA methylation (DNAm) may contribute to processes that underlie associations between air pollution and poor health. Therefore, our objective was to evaluate associations between DNAm and ambient concentrations of particulate matter (PM) =2.5, =10, and 2.5-10 µm in diameter (PM2.5; PM10; PM2.5-10). METHODS: We conducted a methylome-wide association study among twelve cohort- and race/ethnicity-stratified subpopulations from the Women's Health Initiative and the Atherosclerosis Risk i...
Keywords: Epigenetics; Air Pollution; Epigenome-Wide Association Study; Dna Methylation; Particulate Matter
Related Studies: 311, 315, 534, BA23

The association of epigenetic age acceleration and multimorbidity at age 90 in the Women’s Health Initiative

Purva Jain et al., 2022/9 PubMed #36107798 MSID: 4214
Background: Epigenetic age acceleration (EAA), a measure of accelerated biological aging, has been associated with increased risk of several age-related chronic conditions. This is the first study to prospectively examine the relationship between EAA and both multimorbidity count and a weighted multimorbidity score among long-lived postmenopausal women. Methods: We included 1,951 women from the Women's Health Initiative who could have survived to age 90. EAA was estimated using the Horvath pan-t...
Keywords: Epigenetic; Aging; Multimorbidity; Chronic Conditions; Longevity
Related Studies: 311, 315, BA23

Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes

Whitney Leet et al., 2021/12 PubMed #34937574 MSID: 4071
Background: Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) si...
Related Studies: 311, 315, 534, BA23

Association of epigenetic age acceleration with incident mild cognitive impairment and dementia among older women

Aladdin Shadyab et al., 2021/8 PubMed #34417803 MSID: 4146
Background: Epigenetic age acceleration (AgeAccel), which indicates faster biological aging relative to chronological age, has been associated with lower cognitive function. However, the association of AgeAccel with mild cognitive impairment (MCI) or dementia is not well-understood. We examined associations of four AgeAccel measures with incident MCI and dementia. Methods: This prospective analysis included 578 older women from the Women's Health Initiative Memory Study selected for a case-coho...
Keywords: Epigenetics; Dementia; Alzheimer’S; Dna Methylation; Mild Cognitive Impairment; Aging
Related Studies: 311, 315, BA23

Smoking methylation marks for prediction of urothelial cancer risk

Chenglong Yu et al., 2021/9 PubMed #34526299 MSID: 4258
Background: Self-reported information may not accurately capture smoking exposure. We aimed to evaluate whether smoking-associated DNA methylation markers improve urothelial cell carcinoma (UCC) risk prediction. Methods: Conditional logistic regression was used to assess associations between blood-based methylation and UCC risk using two matched case-control samples, N=404 pairs from the Melbourne Collaborative Cohort Study (MCCS) and N=440 pairs from the Women's Health Initiative (WHI) cohort,...
Keywords: Bladder Cancer; Dna Methylation; Smoking; Risk Prediction; Case-Control
Related Studies: 311

AESurv: autoencoder survival analysis for accurate early prediction of coronary heart disease

Yike Shen et al., 2024/9 PubMed #39323093 MSID: 4795
Coronary heart disease (CHD) is one of the leading causes of mortality and morbidity in the United States. Accurate time-to-event CHD prediction models with high-dimensional DNA methylation and clinical features may assist with early prediction and intervention strategies. We developed a state-of-the-art deep learning autoencoder survival analysis model (AESurv) to effectively analyze high-dimensional blood DNA methylation features and traditional clinical risk factors by learning low-dimensiona...
Keywords: Coronary Heart Disease; Autoencoder Survival Analysis; Aesurv; Deep Learning; Prediction
Related Studies: 311, 315, 564, BA23

The role of social determinants of health on epigenetic aging acceleration and symptoms in women cancer survivors: Findings from the Women’s Health Initiative Study

Approved Proposal, Han, Claire J. et al., 2024/7 MSID: 5155
Keywords: Epigenetic Age Acceleration; Dna Methylation; Symptoms; Cancer Survivors; Social Determinants Of Health
Related Studies: 311, 315, BA23

Understanding ADRD disparities using a representative epigenetic clock

Approved Proposal, Boyle, Rory et al., 2024/10 MSID: 5222
Keywords: Epigenetics; Health Equity; Disparities; Dna Methylation; Aging
Related Studies: 311, 315, BA23

Epigenetic entropy, social disparity, and health and lifespan in the Women’s Health Initiative

Approved Manuscript, Mozhui, Khyobeni et al., 2025/1 MSID: 4833
Keywords: Dna Methylation; Epigenetics; Entropy; Aging; Lifespan; Healthspan
Related Studies: 311, 315, BA23

Indoor radon exposure and its effects on leukocyte and platelet traits

Approved Proposal, Shi, Cuiran et al., 2024/6 MSID: 5148
Keywords: Radon; Radiation; Leukocyte; Compositional Data; Platelet
Related Studies: 311, 315, 534, BA23

Mediation by differential DNA methylation of known associations between single nucleotide polymorphisms and bladder cancer risk

Kristina Jordahl et al., 2020/11 PubMed #33213418 MSID: 3659
Background: Though bladder cancer has been the subject of many well-powered genome-wide association studies, the mechanisms involving bladder-cancer-associated single nucleotide polymorphisms (SNPs) remain largely unknown. This study focuses on rs798766, rs401681, rs2294008, and rs8102137, which have been associated with bladder cancer and are also cis-acting methylation quantitative loci (mQTL). Methods: Among 412 bladder cancer cases and 424 controls from the Women's Health Initiative (WHI), w...
Keywords: Dna Methylation; Bladder Cancer; Smoking; Mediation; Epigenetics
Related Studies: 311

Response to a request for cross-examining in WHI successful aging-DNA methylation signatures in ARIC

Approved Proposal, Collins, Jason et al., 2025/4 MSID: 5317
Keywords: Dna; Methylation; Aging; Success; Health; Replication
Related Studies: 311, 315, BA23

DNA methylation in peripheral blood leukocytes for the association with glucose metabolism and invasive breast cancer

Su Yon Jung et al., 2023/2 PubMed #36782224 MSID: 4429
Background: Insulin resistance (IR) is a well-established factor for breast cancer (BC) risk in postmenopausal women, but the interrelated molecular pathways on the methylome are not explicitly described. We conducted a population-level epigenome-wide association (EWA) study for DNA methylation (DNAm) probes that are associated with IR and prospectively correlated with BC development, both overall and in BC subtypes among postmenopausal women. Methods: We used data from Women's Health Initiative...
Keywords: Breast Cancer Risk; Cancer-Related Metabolic Biomarkers; Obesity; Exogenous Estrogen; Dna Methylation
Related Studies: 311, 315, BA23

Pre-cancer epigenetic age acceleration and risk of major adverse cardiovascular events in cancer survivors

Approved Proposal, Vasbinder, Alexi et al., 2025/1 MSID: 5263
Keywords: Cardiovascular Disease; Epigenetics; Accelerated Aging; Cancer; Dna Methylation
Related Studies: 311, 315, BA23

Epigenome-wide meta-analysis of BMI in nine population-based cohorts: examining the utility of epigenetically predicted BMI

Whitney Leet et al., 2023/1 PubMed #36649705 MSID: 4353
This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 17,034), replicated these findings in the Women's Health Initiative (WHI, n = 4,822), and developed an epigenetic prediction score of BMI. In the poole...
Keywords: Obesity; Dna Methylation; Epigenetics; Bmi; Metabolic Health
Related Studies: 311, 315, BA23

Association between Life’s Essential Eight and epigenetic age acceleration

Approved Proposal, Mendoza, Carmen et al., 2023/12 MSID: 5029
Keywords: Life’S Essential Eight; Epigenetics; Cardiovascular Health; Dna Methylation; Biological Aging
Related Studies: 311, 315, BA23

Associations of Epigenetic Age Estimators With Cognitive Function Trajectories in the Women’s Health Initiative Memory Study

Steve Nguyen et al., 2024/7 PubMed #38857479 MSID: 4550
Background and objectives: Epigenetic age estimators indicating faster/slower biological aging vs chronological age independently associate with several age-related outcomes; however, longitudinal associations with cognitive function are understudied. We examined associations of epigenetic age estimators with cognitive function measured annually. Methods: This longitudinal study consisted of older women enrolled in the Women's Health Initiative Memory Study with DNA methylation (DNAm) collected ...
Keywords: Aging; Dna Methylation; Cognitive Functioning; Epigenetic Age Acceleration; Cognitive Aging
Related Studies: 311, 315, BA23

Genome-wide DNA methylation in pre-diagnostic blood and bladder cancer risk in the Women's Health Initiative

Parveen Bhatti et al., 2014/4 PubMed #29540343 MSID: 2895
BACKGROUND: Differential DNA methylation as measured in blood is a promising marker of bladder cancer susceptibility. However, previous studies have exclusively used post-diagnostic blood samples, meaning that observed associations may be markers of disease rather than susceptibility. METHODS: Genome-wide methylation was measured in pre-diagnostic blood samples, using the Illumina Infinium HumanMethylation450 Bead Array, among 440 bladder cancer cases with the transitional cell carcinoma (TCC) s...
Keywords: Bladder Cancer; Papillary Transitional Cell Bladder Cancer; Dna Methylation; Postmenopausal Women; Prediction Model; Risk Factors
Related Studies: 311