0000000000766136
AUTHOR
David M. Herrington
Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies
Background— Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. Methods and Results— Continuous ABI and PAD (ABI ≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ≈2.5 million single nucleotide polymorphisms (SNPs) in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fi…
Common Genetic Variation in Relation to Brachial Vascular Dimensions and Flow-Mediated Vasodilation
Common Genetic Variation in Relation to Brachial Vascular Dimensions and Flow-Mediated Vasodilation
Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure.
Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of pro…
Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease
Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity-associated molecular features that may contribute to obesity-related diseases. Using circulating monocytes from 1,264 Multi-Ethnic Study of Atherosclerosis (MESA) participants, we quantified the transcriptome and epigenome. We discovered that alterations in a network of coexpressed cholesterol metabolism genes are a signature feature of obesity and inflammatory stress. This network included 11 BMI-associated genes related to sterol uptake (↑LDLR, ↓MYLIP), synthesis (↑SCD, FADS1, HMGCS1, FDFT1, SQLE, CYP51A1, SC4MOL), and efflux (↓A…
Associations Between Lipoprotein Subfractions and Area and Density of Abdominal Muscle and Intermuscular Adipose Tissue: The Multi-Ethnic Study of Atherosclerosis
Skeletal muscle quantity and quality decrease with older age, which is partly attributed to ectopic fat infiltration and has negative metabolic consequences. To inform efforts to preserve skeletal muscle with aging, a better understanding of biologic correlates of quantity and quality of muscle and intermuscular adipose tissue (IMAT) is needed. We used targeted lipidomics of lipoprotein subfractions among 947 Multi-Ethnic Study of Atherosclerosis participants to provide a detailed metabolic characterization of area and density of abdominal muscle and IMAT. Serum lipoprotein subfractions were measured at the first visit using 1H-Nuclear Magnetic Resonance spectroscopy. Muscle and IMAT area (…