Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

被引：301

作者：

Soler Artigas, Maria ^{[1
,2
]}

Loth, Daan W. ^{[3
,4
]}

Wain, Louise V. ^{[1
,2
]}

Gharib, Sina A. ^{[5
,6
]}

Obeidat, Ma'en ^{[7
]}

Tang, Wenbo ^{[8
]}

Zhai, Guangju ^{[9
,10
]}

Zhao, Jing Hua ^{[11
]}

Smith, Albert Vernon ^{[12
,13
]}

Huffman, Jennifer E. ^{[14
]}

Albrecht, Eva ^{[15
]}

Jackson, Catherine M. ^{[16
]}

Evans, David M. ^{[17
]}

Cadby, Gemma ^{[18
,19
]}

Fornage, Myriam ^{[20
,21
]}

Manichaikul, Ani ^{[22
,23
]}

Lopez, Lorna M. ^{[24
,25
]}

Johnson, Toby ^{[26
]}

Aldrich, Melinda C. ^{[27
,28
]}

Aspelund, Thor ^{[12
,13
]}

Barroso, Ines ^{[29
,30
]}

Campbell, Harry ^{[31
]}

Cassano, Patricia A. ^{[8
]}

Couper, David J. ^{[32
]}

Eiriksdottir, Gudny ^{[12
]}

Franceschini, Nora ^{[33
]}

Garcia, Melissa ^{[34
]}

Gieger, Christian ^{[15
]}

Gislason, Gauti Kjartan ^{[12
]}

Grkovic, Ivica ^{[35
]}

Hammond, Christopher J. ^{[9
]}

Hancock, Dana B. ^{[36
,37
]}

Harris, Tamara B. ^{[34
]}

Ramasamy, Adaikalavan ^{[38
,39
]}

Heckbert, Susan R. ^{[40
,41
,42
]}

Heliovaara, Markku ^{[43
]}

Homuth, Georg ^{[44
]}

Hysi, Pirro G. ^{[9
]}

James, Alan L. ^{[45
,46
,47
]}

Jankovic, Stipan ^{[35
]}

Joubert, Bonnie R. ^{[36
]}

Karrasch, Stefan ^{[48
]}

Klopp, Norman ^{[49
]}

Koch, Beate ^{[50
]}

Kritchevsky, Stephen B. ^{[51
]}

Launer, Lenore J. ^{[7
]}

Liu, Yongmei ^{[53
]}

Loehr, Laura R. ^{[33
]}

Lohman, Kurt ^{[52
]}

Loos, Ruth J. F. ^{[11
]}

机构：

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

[2] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England

[3] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[4] Inspectorate Healthcare, The Hague, Netherlands

[5] Univ Washington, Ctr Lung Biol, Seattle, WA 98195 USA

[6] Univ Washington, Dept Med, Seattle, WA USA

[7] Univ Nottingham Hosp, Nottingham Resp Biomed Res Unit, Div Therapeut & Mol Med, London, England

[8] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA

[9] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[10] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada

[11] Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England

[12] Iceland Heart Assoc, Kopavogur, Iceland

[13] Univ Iceland, Reykjavik, Iceland

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

[15] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany

[16] Univ St Andrews, Sch Med, St Andrews, Fife, Scotland

[17] Univ Bristol, Sch Social & Community Med, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England

[18] Ontario Inst Canc Res, Toronto, ON, Canada

[19] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada

[20] Univ Texas Houston, Brown Fdn Inst Mol Med, Houston, TX USA

[21] Univ Texas Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA

[22] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA

[23] Univ Virginia, Div Biostat & Epidemiol, Dept Publ Hlth Sci, Charlottesville, VA USA

[24] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[25] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland

[26] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol & Genome Ctr, London, England

[27] Vanderbilt Univ, Dept Thorac Surg, Nashville, TN USA

[28] Vanderbilt Univ, Div Epidemiol, Nashville, TN USA

[29] Wellcome Trust Sanger Inst, Cambridge, England

[30] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England

[31] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland

[32] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA

[33] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA

[34] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA

[35] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia

[36] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA

[37] Res Triangle Inst Int, Behav Hlth Epidemiol Program, Res Triangle Pk, NC USA

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

[39] Kings Coll London, Guys Hosp, Dept Med & Mol Genet, London WC2R 2LS, England

[40] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[41] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[42] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA

[43] Natl Inst Hlth & Welf, Helsinki, Finland

[44] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[45] Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, W Australian Sleep Disorders Res Inst, Nedlands, WA 6009, Australia

[46] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia

[47] Sir Charles Gairdner Hosp, Dept Resp Med, Busselton Populat Med Res Fdn, Nedlands, WA 6009, Australia

[48] Univ Munich, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany

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

[50] Univ Hosp Greifswald, Dept Internal Med B, Greifswald, Germany

来源：

NATURE GENETICS | 2011年 / 43卷 / 11期

基金：

英国生物技术与生命科学研究理事会; 芬兰科学院; 瑞典研究理事会; 英国医学研究理事会; 英国惠康基金; 瑞士国家科学基金会; 美国国家卫生研究院;

关键词：

OBSTRUCTIVE PULMONARY-DISEASE; GENETIC-VARIATION; METAANALYSIS; VARIANTS; RISK; PROTEIN; POLYMORPHISMS; IMPUTATION; MORTALITY; WOMEN;

D O I：

10.1038/ng.941

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

引用

页码：1082 / 1090

页数：9

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