Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

被引：267

作者：

Kato, Norihiro ^{[1
]}

Loh, Marie ^{[2
,3
,4
]}

Takeuchi, Fumihiko ^{[1
]}

Verweij, Niek ^{[5
]}

Wang, Xu ^{[6
,7
]}

Zhang, Weihua ^{[3
,8
]}

Kelly, Tanika N. ^{[9
]}

Saleheen, Danish ^{[10
,11
,12
]}

Lehne, Benjamin ^{[3
]}

Leach, Irene Mateo ^{[5
]}

Drong, Alexander W. ^{[13
]}

Abbott, James ^{[14
]}

Wahl, Simone ^{[15
,16
,17
]}

Tan, Sian-Tsung ^{[8
,18
]}

Scott, William R. ^{[3
,18
]}

Campanella, Gianluca ^{[3
]}

Chadeau-Hyam, Marc ^{[3
]}

Afzal, Uzma ^{[3
,8
]}

Ahluwalia, Tarunveer S. ^{[19
,20
,21
]}

Bonder, Marc Jan ^{[22
]}

Chen, Peng ^{[6
,7
]}

Dehghan, Abbas ^{[23
]}

Edwards, Todd L. ^{[24
]}

Esko, Tonu ^{[25
,26
,27
,28
]}

Go, Min Jin ^{[29
]}

Harris, Sarah E. ^{[30
,31
,32
]}

Hartiala, Jaana ^{[33
,34
]}

Kasela, Silva ^{[25
]}

Kasturiratne, Anuradhani ^{[35
]}

Khor, Chiea-Chuen ^{[6
,7
,36
,37
,38
]}

Kleber, Marcus E. ^{[39
]}

Li, Huaixing ^{[40
]}

Mok, Zuan Yu ^{[41
]}

Nakatochi, Masahiro ^{[42
]}

Sapari, Nur Sabrina ^{[41
]}

Saxena, Richa ^{[43
]}

Stewart, Alexandre F. R. ^{[44
,45
]}

Stolk, Lisette ^{[46
]}

Tabara, Yasuharu ^{[47
]}

Teh, Ai Ling ^{[48
]}

Wu, Ying ^{[49
]}

Wu, Jer-Yuarn ^{[50
,51
]}

Zhang, Yi ^{[52
,53
]}

Aits, Imke ^{[54
]}

Alves, Alexessander Da Silva Couto ^{[55
]}

Das, Shikta ^{[55
]}

Dorajoo, Rajkumar ^{[36
]}

Hopewell, Jemma C. ^{[56
]}

Kim, Yun Kyoung ^{[29
]}

Koivula, Robert W. ^{[57
]}

机构：

[1] Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo, Japan

[2] Univ Oulu, Inst Hlth Sci, Oulu, Finland

[3] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England

[4] ASTAR, Translat Lab Genet Med, Singapore, Singapore

[5] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

[6] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore

[7] Natl Univ Hlth Syst, Singapore, Singapore

[8] Ealing Hosp Natl Hlth Serv NHS Trust, Southall, Middx, England

[9] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA

[10] Ctr Non Communicable Dis, Karachi, Pakistan

[11] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England

[12] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA

[13] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[14] Univ London Imperial Coll Sci Technol & Med, Bioinformat Support Serv, London, England

[15] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany

[16] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany

[17] German Ctr Diabet Res DZD, Neuherberg, Germany

[18] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England

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

[20] Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood COSP, Copenhagen, Denmark

[21] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[22] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[23] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands

[24] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Epidemiol Ctr,Ctr Human Genet Res, Nashville, TN USA

[25] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia

[26] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[27] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

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

[29] Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea

[30] Univ Edinburgh, Med Genet Sect, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland

[31] Western Gen Hosp, Inst Genet & Mol Med, MRC, Edinburgh EH4 2XU, Midlothian, Scotland

[32] Univ Edinburgh, Ctr Cognit Aging & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[33] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[34] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA

[35] Univ Kelaniya, Fac Med, Dept Publ Hlth, Ragama, Sri Lanka

[36] ASTAR, Genome Inst Singapore, Singapore, Singapore

[37] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore

[38] Natl Univ Singapore, Dept Paediat, Singapore 117548, Singapore

[39] Heidelberg Univ, Mannheim Med Fac, Med Clin V, Mannheim, Germany

[40] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China

[41] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore

[42] Nagoya Univ Hosp, Ctr Adv Med & Clin Res, Nagoya, Aichi, Japan

[43] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA

[44] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada

[45] Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada

[46] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands

[47] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan

[48] ASTAR, Singapore Inst Clin Sci, Singapore, Singapore

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

[50] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

来源：

NATURE GENETICS | 2015年 / 47卷 / 11期

基金：

中国国家自然科学基金; 新加坡国家研究基金会; 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; 芬兰科学院; 美国国家卫生研究院; 瑞典研究理事会; 英国惠康基金;

关键词：

RISK-FACTORS; REGIONS; DISEASE; KIDNEY; METAANALYSIS; INDIVIDUALS; PERFORMANCE; POPULATION; EXPRESSION; VARIANTS;

D O I：

10.1038/ng.3405

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 x 10(-11) to 5.0 x 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 x 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

引用

页码：1282 / +

页数：14

共 50 条

[11] Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension
Lu, Xiangfeng
Wang, Laiyuan
Lin, Xu
Huang, Jianfeng
Gu, C. Charles
He, Meian
Shen, Hongbing
He, Jiang
Zhu, Jingwen
Li, Huaixing
Hixson, James E.
Wu, Tangchun
Dai, Juncheng
Lu, Ling
Shen, Chong
Chen, Shufeng
He, Lin
Mo, Zengnan
Hao, Yongchen
Mo, Xingbo
Yang, Xueli
Li, Jianxin
Cao, Jie
Chen, Jichun
Fan, Zhongjie
Li, Ying
Zhao, Liancheng
Li, Hongfan
Lu, Fanghong
Yao, Cailiang
Yu, Lin
Xu, Lihua
Mu, Jianjun
Wu, Xianping
Deng, Ying
Hu, Dongsheng
Zhang, Weidong
Ji, Xu
Guo, Dongshuang
Guo, Zhirong
Zhou, Zhengyuan
Yang, Zili
Wang, Renping
Yang, Jun
Zhou, Xiaoyang
Yan, Weili
Sun, Ningling
Gao, Pingjin
Gu, Dongfeng
HUMAN MOLECULAR GENETICS, 2015, 24 (03) : 865 - 874
[12] Genome-wide association study followed by trans-ancestry meta-analysis identify 17 new risk loci for schizophrenia
Liu, Jiewei
Li, Shiwu
Li, Xiaoyan
Li, Wenqiang
Yang, Yongfeng
Guo, Suqin
Lv, Luxian
Xiao, Xiao
Yao, Yong-Gang
Guan, Fanglin
Li, Ming
Luo, Xiong-Jian
BMC MEDICINE, 2021, 19 (01)
[13] Genome-Wide DNA Methylation Association Study Identifies DNA Methylation Associated with ESKD
Zhou Xiaohong
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2024, 35 (10):
[14] Genome-wide trans-ancestry meta-analysis identifies new susceptibility loci for age-related cortical cataract
Zhao, Wanting
Igo, Rob P.
Yonova-Doing, Ekaterina
Jun, Gyungah
Klaver, Caroline C. W.
Klein, Barbara E. K.
Hammond, Christopher J.
Cheng, Ching-Yu
Wan, Jie Jin
Iyengar, Sudha K.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2016, 57 (12)
[15] Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
Louise V Wain
Germaine C Verwoert
Paul F O'Reilly
Gang Shi
Toby Johnson
Andrew D Johnson
Murielle Bochud
Kenneth M Rice
Peter Henneman
Albert V Smith
Georg B Ehret
Najaf Amin
Martin G Larson
Vincent Mooser
David Hadley
Marcus Dörr
Joshua C Bis
Thor Aspelund
Tõnu Esko
A Cecile J W Janssens
Jing Hua Zhao
Simon Heath
Maris Laan
Jingyuan Fu
Giorgio Pistis
Jian'an Luan
Pankaj Arora
Gavin Lucas
Nicola Pirastu
Irene Pichler
Anne U Jackson
Rebecca J Webster
Feng Zhang
John F Peden
Helena Schmidt
Toshiko Tanaka
Harry Campbell
Wilmar Igl
Yuri Milaneschi
Jouke-Jan Hottenga
Veronique Vitart
Daniel I Chasman
Stella Trompet
Jennifer L Bragg-Gresham
Behrooz Z Alizadeh
John C Chambers
Xiuqing Guo
Terho Lehtimäki
Brigitte Kühnel
Lorna M Lopez
Nature Genetics, 2011, 43 : 1005 - 1011
[16] Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
Wain, Louise V.
Verwoert, Germaine C.
O'Reilly, Paul F.
Shi, Gang
Johnson, Toby
Johnson, Andrew D.
Bochud, Murielle
Rice, Kenneth M.
Henneman, Peter
Smith, Albert V.
Ehret, Georg B.
Amin, Najaf
Larson, Martin G.
Mooser, Vincent
Hadley, David
Doerr, Marcus
Bis, Joshua C.
Aspelund, Thor
Esko, Tonu
Janssens, A. Cecile J. W.
Zhao, Jing Hua
Heath, Simon
Laan, Maris
Fu, Jingyuan
Pistis, Giorgio
Luan, Jian'an
Arora, Pankaj
Lucas, Gavin
Pirastu, Nicola
Pichler, Irene
Jackson, Anne U.
Webster, Rebecca J.
Zhang, Feng
Peden, John F.
Schmidt, Helena
Tanaka, Toshiko
Campbell, Harry
Igl, Wilmar
Milaneschi, Yuri
Hottenga, Jouke-Jan
Vitart, Veronique
Chasman, Daniel I.
Trompet, Stella
Bragg-Gresham, Jennifer L.
Alizadeh, Behrooz Z.
Chambers, John C.
Guo, Xiuqing
Lehtimaki, Terho
Kuehnel, Brigitte
Lopez, Lorna M.
NATURE GENETICS, 2011, 43 (10) : 1005 - U122
[17] MULTI-ANCESTRY GENOME-WIDE ASSOCIATION STUDY IDENTIFIES ATOPIC DERMATITIS LOCI WITH ANCESTRY SPECIFIC EFFECTS
Budu-Aggrey, Ashley
Kilanowski, Anna
Sobczyk, Maria
Tanaka, Nao
Terao, Chikashi
Standl, Marie
German, Chris
Paternoster, Lavinia
ACTA DERMATO-VENEREOLOGICA, 2022, 102 : 41 - 41
[18] Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction (vol 53, pg 65, 2021)
Conti, David V.
Darst, Burcu F.
Moss, Lilit C.
Saunders, Edward J.
Sheng, Xin
Chou, Alisha
Schumacher, Fredrick R.
Al Olama, Ali Amin
Benlloch, Sara
Dadaev, Tokhir
Brook, Mark N.
Sahimi, Ali
Hoffmann, Thomas J.
Takahashi, Atushi
Matsuda, Koichi
Momozawa, Yukihide
Fujita, Masashi
Muir, Kenneth
Lophatananon, Artitaya
Wan, Peggy
Le Marchand, Loic
Wilkens, Lynne R.
Stevens, Victoria L.
Gapstur, Susan M.
Carter, Brian D.
Schleutker, Johanna
Tammela, Teuvo L. J.
Sipeky, Csilla
Auvinen, Anssi
Giles, Graham G.
Southey, Melissa C.
MacInnis, Robert J.
Cybulski, Cezary
Wokolorczyk, Dominika
Lubinski, Jan
Neal, David E.
Donovan, Jenny L.
Hamdy, Freddie C.
Martin, Richard M.
Nordestgaard, Borge G.
Nielsen, Sune F.
Weischer, Maren
Bojesen, Stig E.
Roder, Martin Andreas
Iversen, Peter
Batra, Jyotsna
Chambers, Suzanne
Moya, Leire
Horvath, Lisa
Clements, Judith A.
NATURE GENETICS, 2021, 53 (03) : 413 - 413
[19] Genome-Wide Association Study Identifies Genetic Loci Associated with Iron Deficiency
McLaren, Christine E.
Garner, Chad P.
Constantine, Clare C.
McLachlan, Stela
Vulpe, Chris D.
Snively, Beverly M.
Gordeuk, Victor R.
Nickerson, Debbie A.
Cook, James D.
Leiendecker-Foster, Catherine
Beckman, Kenneth B.
Eckfeldt, John H.
Barcellos, Lisa F.
Murray, Joseph A.
Adams, Paul C.
Acton, Ronald T.
Killeen, Anthony A.
McLaren, Gordon D.
PLOS ONE, 2011, 6 (03):
[20] Genome-Wide Association Study Identifies Genetic Loci Associated with Iron Deficiency
McLaren, Christine E.
Garner, Chad P.
Constantine, Clare C.
Masle, Stela
Vulpe, Christopher D.
Snively, Beverly M.
Cook, James D.
Nickerson, Deborah A.
Leiendecker-Foster, Catherine
Beckman, Kenneth B.
Eckfeldt, John H.
Gordeuk, Victor R.
Murray, Joseph A.
Adams, Paul C.
Barcellos, Lisa F.
Killeen, Anthony A.
Goddard, Katrina
Reboussin, David M.
McLaren, Gordon D.
BLOOD, 2009, 114 (22) : 1552 - 1553

← 1 2 3 4 5 →