Single-Ancestry versus Multi-Ancestry Polygenic Risk Scores for CKD in Black American Populations.

Key Points: The predictive performance of an African ancestry–specific polygenic risk score (PRS) was comparable to a European ancestry–derived PRS for kidney traits. However, multi-ancestry PRSs outperform single-ancestry PRSs in Black American populations. Predictive accuracy of PRSs for CKD was improved with the use of race-free eGFR.

Synthesizing Subject-matter Expertise for Variable Selection in Causal Effect Estimation: A Case Study.

Background: Causal graphs are an important tool for covariate selection but there is limited applied research on how best to create them. Here, we used data from the Coronary Drug Project trial to assess a range of approaches to directed acyclic graph (DAG) creation. We focused on the effect of adherence on mortality in the placebo arm, since the true causal effect is believed with a high degree of certainty.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer's disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole genome sequencing of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.

Neighborhood Disadvantage and Risk of Heart Failure: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Background: Heart failure (HF) affects >6 million US adults, with recent increases in HF hospitalizations. We aimed to investigate the association between neighborhood disadvantage and incident HF events and potential differences by diabetes status.

Methods: We included 23 645 participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), a prospective cohort of Black and White adults aged ≥45 years living in the continental United States (baseline 2005-2007).

Epigenetic age in African American adolescents with type 2 diabetes: A cross-sectional case-control study protocol.

Background And Aims: Type 2 diabetes (T2D) is a disease caused by a relative insulin deficiency compared to the significant insulin requirement needed by the body to achieve glycemic control. T2D in adolescence appears to be increasing in prevalence over the past several decades, necessitating studies to understand for the onset of the disease to occur early in the lifespan. Given the high burden of disease, specifically in young African American adolescents, our study chose to focus initially on feasibility of recruitment of this population.

Epigenetic age acceleration mediates the relationship between neighborhood deprivation and pain severity in adults with or at risk for knee osteoarthritis pain.

An estimated 250 million people worldwide suffer from knee osteoarthritis (KOA), with older adults having greater risk. Like other age-related diseases, residents of high-deprivation neighborhoods experience worse KOA pain outcomes compared to their more affluent neighbors. The purpose of this study was to examine the relationship between neighborhood deprivation and pain severity in KOA and the influence of epigenetic age acceleration (EpAA) on that relationship.

Still Exhausted: The Role of Residual Caregiving Fatigue on Women in Medicine and Science Across the Pipeline.

Understanding the impact of caregiving responsibilities on women in medicine is crucial for ensuring a healthy and intact workforce, as caregiving responsibilities have the potential to affect the careers of women in health care along the entire pipeline, from students and trainees to physicians, physician-scientists, and biomedical researchers.

The CTSA Diversity, Equity, Inclusion, and Accessibility (DEIA) Task Force's recommendations for the CTSA program consortium.

The Clinical and Translational Science Award (CTSA) Program recognizes that advancing diversity, equity, inclusion, and accessibility (DEIA) requires moving beyond statements of commitment to transformative actions. In 2021, the CTSA Program created a Task Force (TF) to initiate work in support of structural and transformational initiatives that advance DEIA for the consortium and its individual hubs. We describe the process of forming the expertise-driven (DEIA) TF and our activities to date.

Investigating Gene-Diet Interactions Impacting the Association Between Macronutrient Intake and Glycemic Traits.

Unlabelled: Few studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed 33,187 participants free of diabetes from 10 National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data.

Obesity and Overweight: Probing Causes, Consequences, and Novel Therapeutic Approaches Through the American Heart Association's Strategically Focused Research Network.

As the worldwide prevalence of overweight and obesity continues to rise, so too does the urgency to fully understand mediating mechanisms, to discover new targets for safe and effective therapeutic intervention, and to identify biomarkers to track obesity and the success of weight loss interventions. In 2016, the American Heart Association sought applications for a Strategically Focused Research Network (SFRN) on Obesity. In 2017, 4 centers were named, including Johns Hopkins University School of Medicine, New York University Grossman School of Medicine, University of Alabama at Birmingham, and Vanderbilt University Medical Center.

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.

Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.

Epigenetic Age Acceleration in Mothers and Offspring 4-10 Years after a Pregnancy Complicated by Gestational Diabetes and Obesity.

A known association exists between exposure to gestational diabetes mellitus (GDM) and epigenetic age acceleration (EAA) in GDM-exposed offspring compared to those without GDM exposure. This association has not been assessed previously in mothers with pregnancies complicated by GDM. A total of 137 mother-child dyads with an index pregnancy 4−10 years before study enrollment were included.

gene interacts with in the development of end-stage kidney disease: A genome-wide association study.

Background: Some but not all African-Americans (AA) who carry nephropathy risk variants () develop kidney failure (end-stage kidney disease, ESKD). To identify genetic modifiers, we assessed gene-gene interactions in a large prospective cohort of the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Methods: Genotypes from 8,074 AA participants were obtained from Illumina Infinium Multi-Ethnic AMR/AFR Extended BeadChip.

Mother-child cardiometabolic health 4-10 years after pregnancy complicated by obesity with and without gestational diabetes.

Objective: Obesity in pregnancy and gestational diabetes (GDM) increase cardiometabolic disease risk but are difficult to disentangle. This study aimed to test the hypothesis that 4-10 years after a pregnancy complicated by overweight/obesity and GDM (OB-GDM), women and children would have greater adiposity and poorer cardiometabolic health than those with overweight/obesity (OB) or normal weight (NW) and no GDM during the index pregnancy.

Methods: In this cross-sectional study, mother-child dyads were stratified into three groups based on maternal health status during pregnancy (OB-GDM = 67; OB = 76; NW = 76).

Recommendations on the use and reporting of race, ethnicity, and ancestry in genetic research: Experiences from the NHLBI TOPMed program.

How race, ethnicity, and ancestry are used in genomic research has wide-ranging implications for how research is translated into clinical care and incorporated into public understanding. Correlation between race and genetic ancestry contributes to unresolved complexity for the scientific community, as illustrated by heterogeneous definitions and applications of these variables. Here, we offer commentary and recommendations on the use of race, ethnicity, and ancestry across the arc of genetic research, including data harmonization, analysis, and reporting.