Medicine and Health Sciences Commons^™

Comprehensive Genetic Analysis Of The Human Lipidome Identifies Loci Associated With Lipid Homeostasis With Links To Coronary Artery Disease, Gemma Cadby, Corey Giles, Phillip E. Melton, Kevin Huynh, Natalie A. Mellett, Thy Duong, Anh Nguyen, Michelle Cinel, Alex Smith, John Blangero

School of Medicine Publications and Presentations

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were …

Apoe Gene Associated With Cholesterol-Related Traits In The Hispanic Population, Stephanie Lozano, Victoria I. Padilla, Manuel Lee Avila, Mario Gil, Gladys E. Maestre, Kesheng Wang, Chun Xu

Health & Biomedical Sciences Faculty Publications and Presentations

Genetic variants in the apolipoprotein E (APOE) gene are associated with lipid metabolism and lipid-related traits in the non-Hispanic population. There have been limited studies regarding the association between the APOE gene and hypercholesterolemia in the Hispanic population; therefore, our aim for this study is to examine the APOE gene’s associations with cholesterol level and its related phenotypes. The APOE gene consists of three different alleles, ε2, ε3, and ε4, with ε4 being associated with dementia and cardiovascular diseases. A total of 1,382 subjects were collected from the Texas Alzheimer’s Research and Care Consortium (TARCC, N = 1320) and the …

New Loci For Body Fat Percentage Reveal Link Between Adiposity And Cardiometabolic Disease Risk, Yingchang Lu, Felix R. Day, Stefan Gustafsson, Martin L. Buchkovich, Jianbo Na, Veronique Bataille, Diana L. Cousminer, Zari Dastani, Joanne E. Curran, John Blangero

School of Medicine Publications and Presentations

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed …

Ambulatory Hypertension Subtypes And 24-Hour Systolic And Diastolic Blood Pressure As Distinct Outcome Predictors In 8341 Untreated People Recruited From 12 Populations, Yan Li, Fang-Fei Wei, Lutgarde Thijs, José Boggia, Kei Asayama, Tine W. Hansen, Masahiro Kikuya, Kristina Björklund-Bodegård, Takayoshi Ohkubo, Gladys E. Maestre

School of Medicine Publications and Presentations

Background—Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce.

Methods and Results—We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs≤1.54; P≥0.18), but was associated with a …