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

Aspasia Angelakopoulou, Tina Shah, Reecha Sofat, Sonia Shah, Diane J. Berry, Jackie Cooper, Jutta Palmen, Ioanna Tzoulaki, Andrew Wong, Barbara J. Jefferis, Nikolas Maniatis, Fotios Drenos, Bruna Gigante, Rebecca Hardy, Ross C. Laxton, Karin Leander, Anna Motterle, Iain A. Simpson, Liam Smeeth, Andy ThomsonClaudio Verzilli, Diana Kuh, Helen Ireland, John Deanfield, Mark Caulfield, Chris Wallace, Nilesh Samani, Patricia B. Munroe, Mark Lathrop, F. Gerry R Fowkes, Michael Marmot, Peter H. Whincup, John C. Whittaker, Ulf De Faire, Mika Kivimaki, Meena Kumari, Elina Hypponen, Chris Power, Steve E. Humphries, Philippa J. Talmud, Jackie Price, Richard W. Morris, Shu Ye, Juan P. Casas, Aroon D. Hingorani

    Research output: Contribution to journalArticlepeer-review

    77 Citations (Scopus)

    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 casecontrol 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 1.111.24) and rs10757274 (OR 1.17; 1.091.26), MIA3 rs17465637 (OR 1.10; 1.041.15), Ch2q36 rs2943634 (OR 1.08; 1.031.14), 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; 0.840.97), an increase in Apolipoprotein AI and HDL-cholesterol, and reduced triglycerides. SORT1 rs599839 was associated with CHD risk (OR 1.20; 1.151.26) 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.

    Original languageEnglish
    Pages (from-to)393-407
    Number of pages15
    JournalEuropean heart journal
    Volume33
    Issue number3
    DOIs
    Publication statusPublished or Issued - Feb 2012

    Keywords

    • Coronary disease
    • Genes
    • Lipids
    • Risk factors

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

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