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


Angelakopoulou, A; Shah, T; Sofat, R; Shah, S; Berry, DJ; Cooper, J; Palmen, J; Tzoulaki, I; Wong, A; Jefferis, BJ; Maniatis, N; Drenos, F; Gigante, B; Hardy, R; Laxton, RC; Leander, K; Motterle, A; Simpson, IA; Smeeth, L; Thomson, A; Verzilli, C; Kuh, D; Ireland, H; Deanfield, J; Caulfield, M; Wallace, C; Samani, N; Munroe, PB; Lathrop, M; Fowkes, FG; Marmot, M; Whincup, PH; Whittaker, JC; de Faire, U; Kivimaki, M; Kumari, M; Hypponen, E; Power, C; Humphries, SE; Talmud, PJ; Price, J; Morris, RW; Ye, S; Casas, JP; Hingorani, AD; (2011) Comparative analysis of genome-wide-association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration. European heart journal. ISSN 0195-668X DOI: https://doi.org/10.1093/eurheartj/ehr225

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Abstract

Aims To 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 results Using 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. Conclusion Several 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.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 21804106
Web of Science ID: 300046100020
URI: http://researchonline.lshtm.ac.uk/id/eprint/322

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