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

Andrew Wong

Andy Thomson

Anna Motterle

Aroon D. Hingorani

Aspasia Angelakopoulou

Barbara J. Jefferis

British Regional Heart Study

Bruna Gigante

Cholesterol Treatment Trialists’ (CTT) Collaboration

Chris Power

Chris Wallace

Claudio Verzilli

Coronary Artery Disease Consortium

Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, ovartis Institutes of BioMedical Research

Diana Kuh

Diane J. Berry

Elina Hypponen

F. Gerry R. Fowkes

Fotios Drenos

Helen Ireland

Iain A. Simpson

Ioanna Tzoulaki

Jackie Cooper

Jackie Price

John C. Whittaker

John Deanfield

Juan P. Casas

Jutta Palmen

Karin Leander

Liam Smeeth

Mark Caulfield

Mark Lathrop

Meena Kumari

Michael Marmot

Mika Kivimaki

Nikolas Maniatis

Nilesh Samani

Patricia B. Munroe

Peter H. Whincup

Philippa J. Talmud

Rebecca Hardy

Reecha Sofat

Richard W. Morris

Ross C. Laxton

Shu Ye

Sonia Shah

Steve E. Humphries

The Wellcome Trust Case Control Consortium

the WTCCC and the Cardiogenics Consortium

Tina Shah

Triglyceride Coronary Disease Genetics Consortium, The Emerging Risk Factors Collaboration

Ulf de Faire

PubMed

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.</p

Angelakopoulou, Aspasia

Shah, Tina

Sofat, Reecha

Shah, Sonia

Berry, Diane J

Cooper, Jackie

Palmen, Jutta

Tzoulaki, Ioanna

Wong, Andrew

Jefferis, Barbara J

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

Explore Bristol Research

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

Edinburgh Research Explorer

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

Berry, Diane J.

Jefferis, Barbara J.

Laxton, Ross C.

Simpson, Iain A.

Munroe, Patricia B.

Fowkes, F. Gerry R.

University of Queensland eSpace

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

Crossref

European Heart Journal

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

St George's Online Research Archive

English

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http://discovery.ucl.ac.uk/1319785/1/Eur_Heart_J-2012-Angelakopoulou-393-407.pdf

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

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