Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration

Abstract

AimsTo evaluate the associations of emergent genome-wide-association study-derived coronary heart disease (CHD)-associated single nucleotide polymorphisms (SNPs) with established and emerging risk factors, and the association of genome-wide-association study-derived lipid-associated SNPs with other risk factors and CHD events.Methods and resultsUsing two case–control studies, three cross-sectional, and seven prospective studies with up to 25 000 individuals and 5794 CHD events we evaluated associations of 34 genome-wide-association study-identified SNPs with CHD risk and 16 CHD-associated risk factors or biomarkers. The Ch9p21 SNPs rs1333049 (OR 1.17; 95% confidence limits 1.11–1.24) and rs10757274 (OR 1.17; 1.09–1.26), MIA3 rs17465637 (OR 1.10; 1.04–1.15), Ch2q36 rs2943634 (OR 1.08; 1.03–1.14), APC rs383830 (OR 1.10; 1.02, 1.18), MTHFD1L rs6922269 (OR 1.10; 1.03, 1.16), CXCL12 rs501120 (OR 1.12; 1.04, 1.20), and SMAD3 rs17228212 (OR 1.11; 1.05, 1.17) were all associated with CHD risk, but not with the CHD biomarkers and risk factors measured. Among the 20 blood lipid-related SNPs, LPL rs17411031 was associated with a lower risk of CHD (OR 0.91; 0.84–0.97), an increase in Apolipoprotein AI and HDL-cholesterol, and reduced triglycerides. SORT1 rs599839 was associated with CHD risk (OR 1.20; 1.15–1.26) as well as total- and LDL-cholesterol, and apolipoprotein B. ANGPTL3 rs12042319 was associated with CHD risk (OR 1.11; 1.03, 1.19), total- and LDL-cholesterol, triglycerides, and interleukin-6.ConclusionSeveral SNPs predicting CHD events appear to involve pathways not currently indexed by the established or emerging risk factors; others involved changes in blood lipids including triglycerides or HDL-cholesterol as well as LDL-cholesterol. The overlapping association of SNPs with multiple risk factors and biomarkers supports the existence of shared points of regulation for these phenotypes.

Genetics of Coronary Artery Disease

“…52 However, 9p21 does not seem to be associated with risk for CAD in blacks. 53 In these studies, as in a more recent study, 54 the 9p21 risk variant is consistently shown to act independently of known risk factors. Fine mapping of the 9p21 risk region shows that it is confined to a 58 000-bp region with several SNPs showing significant association with CAD, all in linkage disequilibrium with rs4977574.…”

Effect of Long-Term Exposure to Lower Low-Densilipoprotein Cholesterol Beginning Early in Life on the Risk of Coronary Heart Disease. A Mendelian Randomization Analysis

“…1) [5,8,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Подробные результаты этих 9 метаанализов представлены на рис.…”

“…В отдельных метаанализах, где объемы выборки не достигали 186000 участников, аллель воздействия для каждого МНП также был связан с соответственно более низким риском ИБС (рис. 2) [8][9][10]17,20,21,[27][28][29][30][31][32][33][34][35][36][37]. Подробные результаты этих 9 метаанализов представ-лены на рис.…”

Tissue expression and predicted protein structures of the bovine ANGPTL3 and association of novel SNPs with growth and meat quality traits

“…ANGPTL3 rs2131925 was associated with a mean reduction in plasma TG levels (Teslovich et al, 2010). In another report, ANGPTL3 rs12042319 was associated with lower levels of low-density lipoprotein cholesterol, TG and IL-6 (Angelakopoulou et al, 2012). These studies clearly showed there is a genetic link between ANGPTL3 and regulation of lipid metabolism, which suggested that variation in ANGPTL3 might affect its function.…”