Newly identified loci that influence lipid concentrations and risk of coronary artery disease

被引：1329

作者：

Willer, Cristen J. ^{[1
]}

Sanna, Serena ^{[1
,2
]}

Jackson, Anne U. ^{[1
]}

Scuteri, Angelo ^{[3
,4
]}

Bonnycastle, Lori L. ^{[5
]}

Clarke, Robert ^{[6
]}

Heath, Simon C. ^{[7
]}

Timpson, Nicholas J. ^{[8
]}

Najjar, Samer S. ^{[3
]}

Stringham, Heather M. ^{[1
]}

Strait, James ^{[3
]}

Duren, William L. ^{[1
]}

Maschio, Andrea ^{[2
]}

Busonero, Fabio ^{[2
]}

Mulas, Antonella ^{[2
]}

Albai, Giuseppe ^{[2
]}

Swift, Amy J. ^{[5
]}

Morken, Mario A. ^{[5
]}

Narisu, Narisu ^{[5
]}

Bennett, Derrick ^{[6
]}

Parish, Sarah ^{[6
]}

Shen, Haiqing ^{[9
]}

Galan, Pilar ^{[10
,11
]}

Meneton, Pierre ^{[12
,13
,14
,15
,16
]}

Hercberg, Serge ^{[12
,13
,14
,15
,16
]}

Zelenika, Diana ^{[7
]}

Chen, Wei-Min ^{[1
]}

Li, Yun ^{[1
]}

Scott, Laura J. ^{[1
]}

Scheet, Paul A. ^{[1
]}

Sundvall, Jouko ^{[17
]}

Watanabe, Richard M. ^{[18
,19
]}

Nagaraja, Ramaiah ^{[3
]}

Ebrahim, Shah ^{[20
]}

Lawlor, Debbie A. ^{[8
]}

Ben-Shlomo, Yoav ^{[8
]}

Davey-Smith, George ^{[8
]}

Shuldiner, Alan R. ^{[9
]}

Collins, Rory ^{[6
]}

Bergman, Richard N. ^{[18
]}

Uda, Manuela ^{[2
]}

Tuomilehto, Jaakko ^{[21
]}

Cao, Antonio ^{[2
]}

Collins, Francis S. ^{[5
]}

Lakatta, Edward ^{[3
]}

Lathrop, G. Mark ^{[7
]}

Boehnke, Michael ^{[1
]}

Schlessinger, David ^{[3
]}

Mohlke, Karen L. ^{[22
]}

Abecasis, Goncalo R. ^{[1
]}

机构：

[1] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[2] Citta Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy

[3] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA

[4] Ist Patol Endocrina & Metab, Unita Operat Geriatr, Rome, Italy

[5] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA

[6] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England

[7] Commissariat Energie Atom, Inst Genom, Ctr Natl Genotypage, F-91057 Evry, France

[8] Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England

[9] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[10] INSERM, U872, F-75270 Paris, France

[11] Fac Med Rene Descartes, Dept Sante Publ & Informat Med, F-75270 Paris, France

[12] CRNH, F-93017 Bobigny, France

[13] INSERM, U557, F-93017 Bobigny, France

[14] INRA, U1125, F-93017 Bobigny, France

[15] Cnam, F-93017 Bobigny, France

[16] Univ Paris 13, F-93017 Bobigny, France

[17] Natl Publ Hlth Inst, Dept Hlth & Funct Capac, Lab Analyt Biochem, SF-00300 Helsinki, Finland

[18] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA

[19] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA

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

[21] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland

[22] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

来源：

NATURE GENETICS | 2008年 / 40卷 / 02期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1038/ng.76

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学]; 090102 [作物遗传育种];

摘要：

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.

引用

页码：161 / 169

页数：9

共 49 条

[1]

A general test of association for quantitative traits in nuclear families [J].

Abecasis, GR ;

Cardon, LR ;

Cookson, WOC .

AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 66 (01) :279-292

[2]

A haplotype map of the human genome [J].

Altshuler, D ;

Brooks, LD ;

Chakravarti, A ;

Collins, FS ;

Daly, MJ ;

Donnelly, P ;

Gibbs, RA ;

Belmont, JW ;

Boudreau, A ;

Leal, SM ;

Hardenbol, P ;

Pasternak, S ;

Wheeler, DA ;

Willis, TD ;

Yu, FL ;

Yang, HM ;

Zeng, CQ ;

Gao, Y ;

Hu, HR ;

Hu, WT ;

Li, CH ;

Lin, W ;

Liu, SQ ;

Pan, H ;

Tang, XL ;

Wang, J ;

Wang, W ;

Yu, J ;

Zhang, B ;

Zhang, QR ;

Zhao, HB ;

Zhao, H ;

Zhou, J ;

Gabriel, SB ;

Barry, R ;

Blumenstiel, B ;

Camargo, A ;

Defelice, M ;

Faggart, M ;

Goyette, M ;

Gupta, S ;

Moore, J ;

Nguyen, H ;

Onofrio, RC ;

Parkin, M ;

Roy, J ;

Stahl, E ;

Winchester, E ;

Ziaugra, L ;

Shen, Y .

NATURE, 2005, 437 (7063) :1299-1320

[3]

[Anonymous], 2004, ATLAS HEART DIS STRO

[4]

Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins [J].

Baigent, C ;

Keech, A ;

Kearney, PM ;

Blackwell, L ;

Buck, G ;

Pollicino, C ;

Kirby, A ;

Sourjina, T ;

Peto, R ;

Collins, R ;

Simes, J .

LANCET, 2005, 366 (9493) :1267-1278

[5]

BAINTON D, 1992, BRIT HEART J, V68, P60

[6]

Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women [J].

Bansal, Sandeep ;

Buring, Julie E. ;

Rifai, Nader ;

Mora, Samia ;

Sacks, Frank M. ;

Ridker, Paul M. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2007, 298 (03) :309-316

[7]

Unique lipoprotein phenotype and genotype associated with exceptional longevity [J].

Barzilai, N ;

Atzmon, G ;

Schechter, C ;

Schaefer, EJ ;

Cupples, AL ;

Lipton, R ;

Cheng, S ;

Shuldiner, AR .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 290 (15) :2030-2040

[8]

Genetics of lipoprotein abnormalities associated with coronary heart disease susceptibility [J].

Breslow, JL .

ANNUAL REVIEW OF GENETICS, 2000, 34 :233-254

[9]

In silico method for inferring genotypes in pedigrees [J].

Burdick, Joshua T. ;

Chen, Wei-Min ;

Abecasis, Goncalo R. ;

Cheung, Vivian G. .

NATURE GENETICS, 2006, 38 (09) :1002-1004

[10]

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

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