Clonal Hematopoiesis and Cardiovascular Outcomes in Older Women.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging aging-related risk factor for cardiovascular disease (CVD). However, previous studies suggest that CHIP's relevance to CVD may diminish with advancing age.

Objectives: This study aimed to test the association of CHIP and its key subtypes with incident CVD in an older population.

Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.

Background: Polygenic risk scores (PRSs) improve type 2 diabetes (T2D) prediction beyond clinical risk factors but perform poorly in non-European populations, where T2D burden is often higher, undermining their global clinical utility.

Methods: We conducted the largest global effort to date to harmonize T2D genome-wide association study (GWAS) meta-analyses across five ancestries-European (EUR), African/African American (AFR), Admixed American (AMR), South Asian (SAS), and East Asian (EAS)-including 360,000 T2D cases and 1·8 million controls (41% non-EUR). We constructed ancestry-specific and multi-ancestry PRSs in training datasets including 11,000 T2D cases and 32,000 controls, and validated their performance in independent datasets including 39,000 T2D cases and 126,000 controls of diverse ancestries.

Association of oil spill cleanup-related hydrocarbon exposure with hypertension and blood pressure in the Gulf Long-term Follow-up Study.

Background: Although several studies have demonstrated a relationship between crude oil exposures and cardiovascular disease, little is known about associations with hypertension.

Objective: Our study examined associations of oil spill cleanup-related benzene, toluene, ethylbenzene, xylene, and n-hexane (BTEX-H) exposures with hypertension prevalence and blood pressure (BP).

Methods: Participants comprised 6693 Deepwater Horizon (DWH) oil spill cleanup and response workers who completed a home visit in the Gulf Long-term Follow-up Study.

Correlates and consequences of clonal hematopoiesis expansion rate: a 16-year longitudinal study of 6976 women.

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased mortality and malignancy risk, yet the determinants of clonal expansion remain poorly understood. We performed sequencing at a depth of coverage of >4000× for CHIP mutations in 6976 postmenopausal women from the Women's Health Initiative (WHI) at 2 time points: the WHI baseline examination and ∼16 years later at the Long Life Study (LLS) visit. Among 3685 CH mutations detected at baseline (variant allele fraction [VAF] of ≥0.

Polypharmacy and Potentially Inappropriate Medications in Adults ≥75 Years of Age by Dementia and Frailty Status: The ARIC Study.

Objective: To estimate the prevalence of polypharmacy (concomitant use of ≥5 medications), hyperpolypharmacy (≥10 medications), and potentially inappropriate medication (PIM) use among older adults according to dementia and frailty status.

Patients And Methods: Cross-sectional data (2016-2017) from 3912 participants aged 71 to 94 years (mean ± SD, 79.6±4.

Metabolomic evaluation of air pollution-related bone damage and potential mediation in Women's Health Initiative participants.

Ambient air pollution has been associated with bone damage. However, no studies have evaluated the metabolomic response to air pollutants and its potential influence on bone health in postmenopausal women. We analyzed data from Women's Health Initiative (WHI) participants with plasma samples.

Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.

Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (n = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping.

How neighborhood socioeconomic status, green space, and walkability are associated with risk for fracture among postmenopausal women.

Although most fractures, and about half of hip fractures, occur outdoors among older women, limited research has uncovered neighborhood predictors for fractures among older women. This study assessed the independent associations of neighborhood socioeconomic status (SES), walkability, and green space with incident any and hip fracture among postmenopausal women. The Women's Health Initiative recruited a national sample of postmenopausal women (50-79 yr) across 40 U.

Methylome-wide association analyses of lipids and modifying effects of behavioral factors in diverse race and ethnicity participants.

Circulating lipid concentrations are clinically associated with cardiometabolic diseases. The phenotypic variance explained by identified genetic variants remains limited, highlighting the importance of searching for additional factors beyond genetic sequence variants. DNA methylation has been linked to lipid concentrations in previous studies, although most of the studies harbored moderate sample sizes and exhibited underrepresentation of non-European ancestry populations.

Correlates and Consequences of Clonal Hematopoiesis Expansion Rate: A 15-Year Longitudinal Study of 6,986 Women.

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased mortality and malignancy risk, yet the determinants of clonal expansion remain poorly understood. We performed sequencing at >4,000x depth of coverage for CHIP mutations in 6,986 postmenopausal women from the Women's Health Initiative at two timepoints approximately 15 years apart. Among 3,685 mutations detected at baseline (VAF ≥ 0.

Racial residential segregation is associated with ambient air pollution exposure after adjustment for multilevel sociodemographic factors: Evidence from eight US-based cohorts.

Objective: We examined if racial residential segregation (RRS) - a fundamental cause of disease - is independently associated with air pollution after accounting for other neighborhood and individual-level sociodemographic factors, to better understand its potential role as a confounder of air pollution-health studies.

Methods: We compiled data from eight large cohorts, restricting to non-Hispanic Black and White urban-residing participants observed at least once between 1999 and 2005. We used 2000 decennial census data to derive a spatial RRS measure (divergence index) and neighborhood socioeconomic status (NSES) index for participants' residing Census tracts, in addition to participant baseline data, to examine associations between RRS and sociodemographic factors (NSES, education, race) and residential exposure to spatiotemporal model-predicted PM and NO levels.

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

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 cancers.

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

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 at baseline (1995-1998) from 3 ancillary studies and were followed up to 13 years.

Identifying the relation between food groups and biological ageing: a data-driven approach.

Background: Heterogeneity in ageing rates drives the need for research into lifestyle secrets of successful agers. Biological age, predicted by epigenetic clocks, has been shown to be a more reliable measure of ageing than chronological age. Dietary habits are known to affect the ageing process.

Aircraft noise exposure and body mass index among female participants in two Nurses' Health Study prospective cohorts living around 90 airports in the United States.

Objective: Aircraft noise exposure is linked to cardiovascular disease risk. One understudied candidate pathway is obesity. This study investigates the association between aircraft noise and obesity among female participants in two prospective Nurses' Health Study (NHS and NHSII) cohorts.

Racial disparities in stroke incidence in the Women's Health Initiative: Exploring biological, behavioral, psychosocial, and social risk factors.

Background: - Disparities in incident stroke risk among women by race and ethnicity persist. Few studies report the distribution and association of stroke risk factors by age group among a diverse sample of women.

Methods: - Data from the Women's Health Initiative (WHI) Observational Study collected between 1993 and 2010 were used to calculate cumulative stroke incidence and incidence rates among non-Hispanic African American (NHAA), non-Hispanic white (NHW), and Hispanic white or African American (HWAA) women by age group in participants aged ≥50 years at baseline (N = 77,247).

Clonal Hematopoiesis and Incident Heart Failure With Preserved Ejection Fraction.

Importance: Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic stem cells with leukemogenic acquired genetic variants, is associated with incident heart failure (HF).

Objective: To evaluate the associations of CHIP and key gene-specific CHIP subtypes with incident HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).

Design, Setting, And Participants: This population-based cohort study included participants from 2 racially diverse prospective cohort studies with uniform HF subtype adjudication: the Jackson Heart Study (JHS) and Women's Health Initiative (WHI).