Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

被引：213

作者：

Surendran, Praveen ^{[1
]}

Drenos, Fotios ^{[2
,3
]}

Young, Robin ^{[1
]}

Warren, Helen ^{[4
,5
]}

Cook, James P. ^{[6
,7
]}

Manning, Alisa K. ^{[8
,9
,10
]}

Grarup, Niels ^{[11
]}

Sim, Xueling ^{[12
,13
,14
]}

Barnes, Daniel R. ^{[1
]}

Witkowska, Kate ^{[4
,5
]}

Staley, James R. ^{[1
]}

Tragante, Vinicius ^{[15
]}

Tukiainen, Taru ^{[8
,9
,16
]}

Yaghootkar, Hanieh ^{[17
]}

Masca, Nicholas ^{[18
,19
]}

Freitag, Daniel F. ^{[1
]}

Ferreira, Teresa ^{[20
]}

Giannakopoulou, Olga ^{[21
]}

Tinker, Andrew ^{[5
,21
]}

Harakalova, Magdalena ^{[15
]}

Mihailov, Evelin ^{[22
]}

Liu, Chunyu ^{[23
,24
]}

Kraja, Aldi T. ^{[25
,26
]}

Nielsen, Sune Fallgaard ^{[27
]}

Rasheed, Asif ^{[28
]}

Samue, Maria ^{[28
]}

Zhao, Wei ^{[29
]}

Bonnycastle, Lori L. ^{[30
]}

Jackson, Anne U. ^{[12
,13
]}

Narisu, Narisu ^{[30
]}

Swift, Amy J. ^{[30
]}

Southam, Lorraine ^{[20
,31
]}

Marten, Jonathan ^{[32
]}

Huyghe, Jeroen R. ^{[12
,13
]}

Stancakova, Alena ^{[33
,34
]}

Fava, Cristiano ^{[35
,36
]}

Ohlsson, Therese ^{[35
]}

Matchan, Angela ^{[31
]}

Stirrups, Kathleen E. ^{[21
,37
]}

Bork-Jensen, Jette ^{[11
]}

Gjesing, Anette P. ^{[11
]}

Kontto, Jukka ^{[38
]}

Perola, Markus ^{[22
,38
,39
]}

Shaw-Hawkins, Susan ^{[4
]}

Havulinna, Aki S. ^{[38
]}

Zhang, He ^{[40
]}

Donnelly, Louise A. ^{[41
]}

Groves, Christopher J. ^{[42
]}

Rayner, N. William ^{[20
,31
,42
]}

Neville, Matt J. ^{[42
,43
]}

机构：

[1] Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England

[2] Univ Bristol, Sch Social & Community Med, Med Res Council Integrat Epidemiol Unit, Oakfield House, Bristol, Avon, England

[3] UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England

[4] Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England

[5] Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England

[6] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England

[7] Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England

[8] Harvard Med Sch, Dept Genet, Boston, MA USA

[9] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[10] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[11] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

[12] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[13] Univ Michigan, Dept Biostat, Ann Arbor, MI USA

[14] Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore

[15] Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands

[16] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[17] Univ Exeter, Inst Biomed & Clin Sci, Genet Complex Traits, Sch Med, Exeter, Devon, England

[18] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England

[19] Natl Inst Hlth, Res Leicester Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England

[20] Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England

[21] Queen Mary Univ London, William Harvey Res Inst, Bads & London Sch Med & Dent, Ctr Heart, London, England

[22] Univ Tartu, Estonian Genome Ctr, Tartu, Estonia

[23] NHLBI, Framingham, MA USA

[24] Boston Univ, Framingham Heart Study, Framingham, MA USA

[25] Washington Univ, Ctr Genome Sci & Syst Biol, Div Stat Genom, Sch Med, St Louis, MO USA

[26] Washington Univ, Dept Genet, Sch Med, St Louis, MO USA

[27] Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, Herlev, Denmark

[28] Ctr Noncommunicable Dis, Karachi, Pakistan

[29] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA

[30] NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA

[31] Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England

[32] Univ Edinburgh, Med Res Council Human Genet Unit, Med Res Council Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland

[33] Univ Eastern Finland, Dept Med, Kuopio, Finland

[34] Kuopio Univ Hosp, Kuopio, Finland

[35] Lund Univ, Dept Clin Sci, Malmo, Sweden

[36] Univ Verona, Dept Med, Verona, Italy

[37] Univ Cambridge, Dept Haematol, Cambridge, England

[38] Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland

[39] Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland

[40] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA

[41] Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Dundee, Scotland

[42] Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England

[43] Oxford Univ Hosp Trusts, Natl Inst Hlth, Res Oxford Biomed Res Ctr, Oxford, England

[44] Imperial Coll London, Sect Invest Med, London, England

[45] Brunel Univ London, Dept Life Sci, London, England

[46] Univ Oulu, Inst Biomed, Bioctr Oulu, Oulu, Finland

[47] Poznan Univ Med Sci, Dept Gastroenterol & Metab, Poznan, Poland

[48] Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland

[49] Univ Helsinki, Helsinki, Finland

[50] Oulu Univ Hosp, Dept Obstet & Gynaecol, Oulu, Finland

来源：

NATURE GENETICS | 2016年 / 48卷 / 10期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; AGING RESEARCH; PLASMA-LEVELS; RISK-FACTORS; LOCI; CHARGE; HEART; IDENTIFICATION; ARCHITECTURE;

D O I：

10.1038/ng.3654

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low frequency and common genetic variants in up to 192,763 individuals and used similar to 155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

引用

页码：1151 / 1161

页数：11

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