Common and rare genetic markers of lipid variation in subjects with type 2 diabetes from the ACCORD clinical trial

Autor: Skylar W. Marvel, Daniel M. Rotroff, Michael J. Wagner, John B. Buse, Tammy M. Havener, Howard L. McLeod, Alison A. Motsinger-Reif, The ACCORD/ACCORDion Investigators
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: PeerJ, Vol 5, p e3187 (2017)
Druh dokumentu: article
ISSN: 2167-8359
DOI: 10.7717/peerj.3187
Popis: Background Individuals with type 2 diabetes are at an increased risk of cardiovascular disease. Alterations in circulating lipid levels, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) are heritable risk factors for cardiovascular disease. Here we conduct a genome-wide association study (GWAS) of common and rare variants to investigate associations with baseline lipid levels in 7,844 individuals with type 2 diabetes from the ACCORD clinical trial. Methods DNA extracted from stored blood samples from ACCORD participants were genotyped using the Affymetrix Axiom Biobank 1 Genotyping Array. After quality control and genotype imputation, association of common genetic variants (CV), defined as minor allele frequency (MAF) ≥ 3%, with baseline levels of TC, LDL, HDL, and TG was tested using a linear model. Rare variant (RV) associations (MAF < 3%) were conducted using a suite of methods that collapse multiple RV within individual genes. Results Many statistically significant CV (p
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