Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration.
Angelakopoulou, Aspasia;
Shah, Tina;
Sofat, Reecha;
Shah, Sonia;
Berry, Diane J;
Cooper, Jackie;
Palmen, Jutta;
Tzoulaki, Ioanna;
Wong, Andrew;
Jefferis, Barbara J;
+35 more...Maniatis, Nikolas;
Drenos, Fotios;
Gigante, Bruna;
Hardy, Rebecca;
Laxton, Ross C;
Leander, Karin;
Motterle, Anna;
Simpson, Iain A;
Smeeth, Liam;
Thomson, Andy;
Verzilli, Claudio;
Kuh, Diana;
Ireland, Helen;
Deanfield, John;
Caulfield, Mark;
Wallace, Chris;
Samani, Nilesh;
Munroe, Patricia B;
Lathrop, Mark;
Fowkes, F Gerry R;
Marmot, Michael;
Whincup, Peter H;
Whittaker, John C;
de Faire, Ulf;
Kivimaki, Mika;
Kumari, Meena;
Hypponen, Elina;
Power, Chris;
Humphries, Steve E;
Talmud, Philippa J;
Price, Jackie;
Morris, Richard W;
Ye, Shu;
Casas, Juan P;
Hingorani, Aroon D;
(2011)
Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration.
European heart journal, 33 (3).
pp. 393-407.
ISSN 0195-668X
DOI: https://doi.org/10.1093/eurheartj/ehr225
Permanent Identifier
Use this Digital Object Identifier when citing or linking to this resource.
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.
