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

Angelakopoulou, A./ Shah, T./ Sofat, R./ Shah, S./ Berry, D. J./ Cooper, J./ Palmen, J./ Tzoulaki, I./ Wong, A./ Jefferis, B. J./ Maniatis, N./ Drenos, F./ Gigante, B./ Hardy, R./ Laxton, R. C./ Leander, K./ Motterle, A./ Simpson, I. A./ Smeeth, L./ Thomson, A./ Verzilli, C./ Kuh, D./ Ireland, H./ Deanfield, J./ Caulfield, M./ Wallace, C./ Samani, N./ Munroe, P. B./ Lathrop, M./ Fowkes, F. G./ Marmot, M./ Whincup, P. H./ Whittaker, J. C./ de Faire, U./ Kivimaki, M./ Kumari, M./ Hypponen, E./ Power, C./ Humphries, S. E./ Talmud, P. J./ Price, J./ Morris, R. W./ Ye, S./ Casas, J. P./ Hingorani, A. D.

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Adult,Aged,Biological Markers/blood,Body Mass Index,Case-Control Studies,Coronary Disease/blood/*genetics,Diabetes Mellitus, Type 2/blood/*genetics,Diabetic Cardiomyopathies/blood/*genetics,Female,Genome-Wide Association Study,Humans,Lipids/*blood,Male,Middle Aged,Polymorphism, Single Nucleotide/*genetics,Prospective Studies,Risk Factors
ISSN: 1522-9645
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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