Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

被引：1576

作者：

Ehret, Georg B. ^{[1
,2
,3
,4
]}

Munroe, Patricia B. ^{[5
]}

Rice, Kenneth M. ^{[6
]}

Bochud, Murielle ^{[2
,3
]}

Johnson, Andrew D. ^{[7
,8
]}

Chasman, Daniel I. ^{[9
]}

Smith, Albert V. ^{[10
,11
]}

Tobin, Martin D. ^{[12
]}

Verwoert, Germaine C. ^{[13
,14
,15
]}

Hwang, Shih-Jen ^{[7
,8
,16
]}

Pihur, Vasyl ^{[1
]}

Vollenweider, Peter ^{[17
]}

O'Reilly, Paul F. ^{[18
]}

Amin, Najaf ^{[13
]}

Bragg-Gresham, Jennifer L. ^{[19
]}

Teumer, Alexander ^{[20
]}

Glazer, Nicole L. ^{[21
,22
,23
]}

Launer, Lenore ^{[24
]}

Zhao, Jing Hua ^{[25
]}

Aulchenko, Yurii ^{[13
]}

Heath, Simon ^{[26
]}

Sober, Siim ^{[27
]}

Parsa, Afshin ^{[28
]}

Luan, Jian'an ^{[25
]}

Arora, Pankaj ^{[29
]}

Dehghan, Abbas ^{[13
,14
,15
]}

Zhang, Feng ^{[30
]}

Lucas, Gavin ^{[31
]}

Hicks, Andrew A. ^{[32
,33
]}

Jackson, Anne U. ^{[34
]}

Peden, John F. ^{[35
]}

Tanaka, Toshiko ^{[36
]}

Wild, Sarah H. ^{[37
]}

Rudan, Igor ^{[37
,38
,39
]}

Igl, Wilmar ^{[40
]}

Milaneschi, Yuri ^{[36
]}

Parker, Alex N. ^{[41
]}

Fava, Cristiano ^{[42
,43
]}

Chambers, John C. ^{[18
,44
]}

Fox, Ervin R. ^{[45
]}

Kumari, Meena ^{[46
]}

Go, Min Jin ^{[47
]}

van der Harst, Pim ^{[48
]}

Kao, Wen Hong Linda ^{[49
,50
]}

Sjogren, Marketa ^{[42
]}

Vinay, D. G. ^{[51
]}

Alexander, Myriam ^{[52
]}

Tabara, Yasuharu ^{[53
,54
]}

Shaw-Hawkins, Sue ^{[5
]}

Whincup, Peter H. ^{[55
]}

机构：

[1] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD 21205 USA

[2] CHU Vaudois, Inst Social & Prevent Med IUMSP, CH-1005 Lausanne, Switzerland

[3] Univ Lausanne, CH-1005 Lausanne, Switzerland

[4] Univ Hosp Geneva, Dept Specialties Internal Med, CH-1211 Geneva 14, Switzerland

[5] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Genome Ctr, London EC1M 6BQ, England

[6] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[7] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA

[8] NHLBI, Bethesda, MD 20824 USA

[9] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA

[10] Univ Iceland, IS-101 Reykajvik, Iceland

[11] Iceland Heart Assoc, IS-201 Kopavogur, Iceland

[12] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England

[13] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands

[14] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands

[15] NGI, NCHA, NL-3000 CA Rotterdam, Netherlands

[16] NHLBI, Ctr Populat Studies, Bethesda, MD 20824 USA

[17] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland

[18] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, London W2 1PG, England

[19] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48103 USA

[20] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, D-17487 Greifswald, Germany

[21] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA

[22] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA

[23] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA

[24] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA

[25] Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England

[26] Commiss Energie Atom, Inst Genom, Ctr Natl Genotypage, F-91057 Evry, France

[27] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia

[28] Univ Maryland, Sch Med, Baltimore, MD 21201 USA

[29] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Boston, MA 02114 USA

[30] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England

[31] Inst Municipal Invest Med, E-08003 Barcelona, Spain

[32] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy

[33] Univ Lubeck, Affiliated Inst, Lubeck, Germany

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

[35] Univ Oxford, Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford OX3 7BN, England

[36] NIA, Clin Res Branch, Baltimore, MD 21250 USA

[37] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland

[38] Univ Edinburgh, Coll Med & Vet Med, Inst Genet & Mol Med, Edinburgh EH8 9AG, Midlothian, Scotland

[39] Univ Split, Croatian Ctr Global Hlth, Split 21000, Croatia

[40] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden

[41] Amgen Inc, Cambridge, MA 02139 USA

[42] Lund Univ, Dept Clin Sci, S-20502 Malmo, Sweden

[43] Univ Verona, Dept Med, I-37134 Verona, Italy

[44] Ealing Gen Hosp, London UB1 3HJ, England

[45] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA

[46] UCL, Genet Epidemiol Grp, London WC1E 6BT, England

[47] Natl Inst Hlth, Ctr Genome Sci, Seoul 122701, South Korea

[48] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 GZ Groningen, Netherlands

[49] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA

[50] Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA

来源：

NATURE | 2011年 / 478卷 / 7367期

关键词：

GENOME-WIDE ASSOCIATION; COMMON VARIANTS; HYPERTENSION; LOCI; METAANALYSIS; POPULATION; CLONING; HEALTH;

D O I：

10.1038/nature10405

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

引用

页码：103 / 109

页数：7

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