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

被引：93

作者：

Angelakopoulou, Aspasia ^{[2
]}

Shah, Tina ^{[1
]}

Sofat, Reecha ^{[1
]}

Shah, Sonia ^{[3
]}

Berry, Diane J. ^{[4
,5
]}

Cooper, Jackie ^{[6
]}

Palmen, Jutta ^{[6
]}

Tzoulaki, Ioanna ^{[7
,8
]}

Wong, Andrew ^{[9
]}

Jefferis, Barbara J. ^{[10
]}

Maniatis, Nikolas ^{[11
]}

Drenos, Fotios ^{[6
]}

Gigante, Bruna ^{[12
]}

Hardy, Rebecca ^{[9
]}

Laxton, Ross C. ^{[13
]}

Leander, Karin ^{[12
]}

Motterle, Anna ^{[13
]}

Simpson, Iain A. ^{[14
]}

Smeeth, Liam ^{[2
]}

Thomson, Andy ^{[10
]}

Verzilli, Claudio ^{[2
]}

Kuh, Diana ^{[9
]}

Ireland, Helen ^{[6
]}

Deanfield, John

Caulfield, Mark ^{[13
]}

Wallace, Chris ^{[13
,15
]}

Samani, Nilesh ^{[16
,17
]}

Munroe, Patricia B. ^{[13
]}

Lathrop, Mark ^{[18
]}

Fowkes, F. Gerry R. ^{[19
]}

Marmot, Michael ^{[20
]}

Whincup, Peter H. ^{[21
]}

Whittaker, John C. ^{[2
,22
]}

de Faire, Ulf ^{[12
]}

Kivimaki, Mika ^{[20
]}

Kumari, Meena ^{[20
]}

Hypponen, Elina ^{[4
,5
]}

Power, Chris ^{[4
,5
]}

Humphries, Steve E. ^{[6
]}

Talmud, Philippa J. ^{[6
]}

Price, Jackie ^{[19
]}

Morris, Richard W. ^{[10
]}

Ye, Shu ^{[13
]}

Casas, Juan P. ^{[2
,20
]}

Hingorani, Aroon D. ^{[1
,20
]}

机构：

[1] UCL, Rayne Inst, Ctr Clin Pharmacol, Div Med, London WC1E 6JF, England

[2] Univ London London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England

[3] UCL, UCL Genet Inst, Dept Genet Evolut & Environm, London WC1E 6BT, England

[4] UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London WC1N 1EH, England

[5] UCL, MRC Ctr Epidemiol Child Hlth, Inst Child Hlth, London WC1N 1EH, England

[6] UCL, Rayne Inst, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London WC1E 6JF, England

[7] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London W2 1PG, England

[8] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece

[9] MRC Unit Lifelong Hlth & Ageing, London WC1B 5JU, England

[10] UCL, Sch Med, Dept Primary Care & Populat Hlth, London NW3 2PF, England

[11] UCL, Dept Genet Evolut & Environm, Div Biosci, London WC1E 6BT, England

[12] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden

[13] Queen Mary Univ London, John Vane Sci Ctr, Barts & London Sch Med, William Harvey Res Inst, London EC1M 6BQ, England

[14] Southampton Univ Hosp, Wessex Reg Cardiac Unit, Southampton SO16 6YD, Hants, England

[15] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, JDRF WT Diabet & Inflammat Lab, Cambridge CB2 0XY, England

[16] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England

[17] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England

[18] Ctr Natl Genotypage, F-91057 Paris, France

[19] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland

[20] UCL, Div Populat Hlth, Dept Epidemiol & Publ Hlth, London WC1E 7HB, England

[21] Univ London, Div Community Hlth Sci, London SW17 0RE, England

[22] GlaxoSmithKline, Med Res Ctr, Stevenage SG1 2NY, Herts, England

来源：

EUROPEAN HEART JOURNAL | 2012年 / 33卷 / 03期

基金：

英国惠康基金; 英国经济与社会研究理事会; 英国医学研究理事会;

关键词：

Coronary disease; Lipids; Genes; Risk factors; DENSITY-LIPOPROTEIN CHOLESTEROL; NEWLY IDENTIFIED LOCI; APOLIPOPROTEIN-A-V; ARTERY-DISEASE; FTO GENE; COHORT PROFILE; RISK; TRIGLYCERIDES; VARIANTS; POLYMORPHISMS;

D O I：

10.1093/eurheartj/ehr225

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：393 / 407

页数：15

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