Influence of Genetic Ancestry on Gene-Environment Interactions of Polygenic Risk and Sociocultural Factors: Results from the Hispanic Community Health Study/Study of Latinos.

Background: Many present analyses of Hispanic/Latino populations in epidemiologic research aggregate all members of this ethnic group, despite immense diversity in genetic backgrounds, environment, and culture between and across Hispanic/Latino background groups. Using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we examined the role of self-identified background group and genetic ancestry proportions in gene-environment interactions influencing the relationship between body mass index (BMI) and a polygenic score for BMI (PGS).

Methods: Weighted univariate and multivariable generalized linear models were executed to compare the effects of environmental variables identified by McArdle et al.

A genome-wide association study identifies genetic determinants of hemoglobin glycation index with implications across sex and ethnicity.

Introduction: We investigated the genetic determinants of variation in the hemoglobin glycation index (HGI), an emerging biomarker for the risk of diabetes complications.

Methods: We conducted a genome-wide association study (GWAS) for HGI in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial ( = 7,913) using linear regression and additive genotype encoding on variants with minor allele frequency greater than 3%. We conducted replication analyses of top findings in the Atherosclerosis Risk in Communities (ARIC) study with inverse variance-weighted meta-analysis.

Longitudinal lipidomic profiles of left ventricular mass and left ventricular hypertrophy in American Indians.

BACKGROUNDLeft ventricular hypertrophy (LVH) and dyslipidemia are strong, independent predictors for cardiovascular disease, but their relationship is less well studied. A longitudinal lipidomic profiling of left ventricular mass (LVM) and LVH is still lacking.METHODSUsing liquid chromatography-mass spectrometry (LC-MS), we repeatedly measured 1,542 lipids from 1,755 unique American Indians attending 2 exams (mean, 5 years apart).

Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease.

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

Methods: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing.

Novel Metabolites Associated With Blood Pressure After Dietary Interventions.

Background: The blood pressure (BP) etiologic study is complex due to multifactorial influences, including genetic, environmental, lifestyle, and their intricate interplays. We used a metabolomics approach to capture internal pathways and external exposures and to study BP regulation mechanisms after well-controlled dietary interventions.

Methods: In the ProBP trail (Protein and Blood Pressure), a double-blinded crossover randomized controlled trial, participants underwent dietary interventions of carbohydrate, soy protein, and milk protein, receiving 40 g daily for 8 weeks, with 3-week washout periods.

Associations of Epigenetic Age Acceleration With CVD Risks Across the Lifespan: The Bogalusa Heart Study.

Although epigenetic age acceleration (EAA) might serve as a molecular signature of childhood cardiovascular disease (CVD) risk factors and further promote midlife subclinical CVD, few studies have comprehensively examined these life course associations. This study sought to test whether childhood CVD risk factors predict EAA in adulthood and whether EAA mediates the association between childhood CVD risks and midlife subclinical disease. Among 1,580 Bogalusa Heart Study participants, we estimated extrinsic EAA, intrinsic EAA, PhenoAge acceleration (PhenoAgeAccel), and GrimAge acceleration (GrimAgeAccel) during adulthood.

Clonal hematopoiesis of indeterminate potential contributes to accelerated chronic kidney disease progression.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with stronger associations for CHIP driven by mutations in genes other than (non- CHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways.

A longitudinal study of polygenic score and cognitive function decline considering baseline cognitive function, lifestyle behaviors, and diabetes among middle-aged and older US adults.

Background: Genomic study of cognition decline while considering baseline cognition and lifestyle behaviors is scarce. We aimed to evaluate the impact of a polygenic score for general cognition on cognition decline rate, while considering baseline cognition and lifestyle behaviors, among the general population and people with diabetes, a patient group commonly affected by cognition impairment.

Methods: We tested associations of the polygenic score for general cognition with annual changing rates of cognition measures in 8 years of follow-up among 12,090 White and 3100 Black participants of the Health and Retirement Study (HRS), a nationally representative sample of adults aged 50 years and older in the USA.

Clonal haematopoiesis, ageing and kidney disease.

Clonal haematopoiesis of indeterminate potential (CHIP) is a preclinical condition wherein a sizeable proportion of an individual's circulating blood cells are derived from a single mutated haematopoietic stem cell. CHIP occurs frequently with ageing - more than 10% of individuals over 65 years of age are affected - and is associated with an increased risk of disease across several organ systems and premature death. Emerging evidence suggests that CHIP has a role in kidney health, including associations with predisposition to acute kidney injury, impaired recovery from acute kidney injury and kidney function decline, both in the general population and among those with chronic kidney disease.

Examination of Serum Metabolome Altered by Dietary Carbohydrate, Milk Protein, and Soy Protein Interventions Identified Novel Metabolites Associated with Blood Pressure: The ProBP Trial.

Scope: This study aims to discover metabolites of dietary carbohydrate, soy and milk protein supplements and evaluate their roles in blood pressure (BP) regulation in the protein and blood pressure (ProBP), a cross-over trial.

Methods And Results: Plasma metabolites are profiled at pre-trial baseline and after 8 weeks of supplementation with carbohydrate, soy protein, and milk protein, respectively, among 80 ProBP participants. After Bonferroni correction (α = 6.

Serum Metabolomic Markers of Dairy Consumption: Results from the Atherosclerosis Risk in Communities Study and the Bogalusa Heart Study.

Background: Dairy consumption is related to chronic disease risk; however, the measurement of dairy consumption has largely relied upon self-report. Untargeted metabolomics allows for the identification of objective markers of dietary intake.

Objectives: We aimed to identify associations between dietary dairy intake (total dairy, low-fat dairy, and high-fat dairy) and serum metabolites in 2 independent study populations of United States adults.

Genomic Innovation in Early Life Cardiovascular Disease Prevention and Treatment.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Although CVD events do not typically manifest until older adulthood, CVD develops gradually across the life-course, beginning with the elevation of risk factors observed as early as childhood or adolescence and the emergence of subclinical disease that can occur in young adulthood or midlife. Genomic background, which is determined at zygote formation, is among the earliest risk factors for CVD.

Effects of epigenetic age acceleration on kidney function: a Mendelian randomization study.

Background: Previous studies have reported cross-sectional associations between measures of epigenetic age acceleration (EAA) and kidney function phenotypes. However, the temporal and potentially causal relationships between these variables remain unclear. We conducted a bidirectional two-sample Mendelian randomization study of EAA and kidney function.

Novel Genetic Variants Associated with Chronic Kidney Disease Progression.

Significance Statement: eGFR slope has been used as a surrogate outcome for progression of CKD. However, genetic markers associated with eGFR slope among patients with CKD were unknown. We aimed to identify genetic susceptibility loci associated with eGFR slope.

Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing.

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS.

Emerging evidence on the role of clonal hematopoiesis of indeterminate potential in chronic kidney disease.

Chronic kidney disease (CKD) was responsible for 1.2 million deaths globally in 2016. Despite the large and growing burden of CKD, treatment options are limited and generally only preserve kidney function.