Abstract
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 ×-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.
| Original language | English |
|---|---|
| Pages (from-to) | 1082-1090 |
| Number of pages | 9 |
| Journal | Nature Genetics |
| Volume | 43 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2011 |
ASJC Scopus subject areas
- Genetics
Access to Document
Other files and links
Fingerprint
Dive into the research topics of 'Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function'. Together they form a unique fingerprint.Cite this
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. / Artigas, María Soler; Loth, Daan W.; Wain, Louise V.; Gharib, Sina A.; Obeidat, Ma'En; Tang, Wenbo; Zhai, Guangju; Zhao, Jing Hua; Smith, Albert Vernon; Huffman, Jennifer E.; Albrecht, Eva; Jackson, Catherine M.; Evans, David M.; Cadby, Gemma; Fornage, Myriam; Manichaikul, Ani; Lopez, Lorna M.; Johnson, Toby; Aldrich, Melinda C.; Aspelund, Thor; Barroso, Ins; Campbell, Harry; Cassano, Patricia A.; Couper, David J.; Eiriksdottir, Gudny; Franceschini, Nora; Garcia, Melissa; Gieger, Christian; Gislason, Gauti Kjartan; Grkovic, Ivica; Hammond, Christopher J.; Hancock, Dana B.; Harris, Tamara B.; Ramasamy, Adaikalavan; Heckbert, Susan R.; Heliövaara, Markku; Homuth, Georg; Hysi, Pirro G.; James, Alan L.; Jankovic, Stipan; Joubert, Bonnie R.; Karrasch, Stefan; Klopp, Norman; Koch, Beate; Kritchevsky, Stephen B.; Launer, Lenore J.; Liu, Yongmei; Loehr, Laura R.; Lohman, Kurt; Loos, Ruth J.F.; Lumley, Thomas; Al Balushi, Khalid A.; Ang, Wei Q.; Barr, R. Graham; Beilby, John; Blakey, John D.; Boban, Mladen; Boraska, Vesna; Brisman, Jonas; Britton, John R.; Brusselle, Guy G.; Cooper, Cyrus; Curjuric, Ivan; Dahgam, Santosh; Deary, Ian J.; Ebrahim, Shah; Eijgelsheim, Mark; Francks, Clyde; Gaysina, Darya; Granell, Raquel; Gu, Xiangjun; Hankinson, John L.; Hardy, Rebecca; Harris, Sarah E.; Henderson, John; Henry, Amanda; Hingorani, Aroon D.; Hofman, Albert; Holt, Patrick G.; Hui, Jennie; Hunter, Michael L.; Imboden, Medea; Jameson, Karen A.; Kerr, Shona M.; Kolcic, Ivana; Kronenberg, Florian; Liu, Jason Z.; Marchini, Jonathan; McKeever, Tricia; Morris, Andrew D.; Olin, Anna Carin; Porteous, David J.; Postma, Dirkje S.; Rich, Stephen S.; Ring, Susan M.; Rivadeneira, Fernando; Rochat, Thierry; Sayer, Avan Aihie; Sayers, Ian; Sly, Peter D.; Smith, George Davey; Sood, Akshay; Starr, John M.; Uitterlinden, André G.; Vonk, Judith M.; Wannamethee, S. Goya; Whincup, Peter H.; Wijmenga, Cisca; Williams, O. Dale; Wong, Andrew; Mangino, Massimo; Marciante, Kristin D.; McArdle, Wendy L.; Meibohm, Bernd; Morrison, Alanna C.; North, Kari E.; Omenaas, Ernst; Palmer, Lyle J.; Pietiläinen, Kirsi H.; Pin, Isabelle; Polašek, Ozren; Pouta, Anneli; Psaty, Bruce M.; Hartikainen, Anna Liisa; Rantanen, Taina; Ripatti, Samuli; Rotter, Jerome I.; Rudan, Igor; Rudnicka, Alicja R.; Schulz, Holger; Shin, So Youn; Spector, Tim D.; Surakka, Ida; Vitart, Veronique; Völzke, Henry; Wareham, Nicholas J.; Warrington, Nicole M.; Wichmann, H. Erich; Wild, Sarah H.; Wilk, Jemma B.; Wjst, Matthias; Wright, Alan F.; Zgaga, Lina; Zemunik, Tatijana; Pennell, Craig E.; Nyberg, Fredrik; Kuh, Diana; Holloway, John W.; Boezen, H. Marike; Lawlor, Debbie A.; Morris, Richard W.; Probst-Hensch, Nicole; Kaprio, Jaakko; Wilson, James F.; Hayward, Caroline; Kähönen, Mika; Heinrich, Joachim; Musk, Arthur W.; Jarvis, Deborah L.; Gläser, Sven; Järvelin, Marjo Riitta; Ch Stricker, Bruno H.; Elliott, Paul; O'Connor, George T.; Strachan, David P.; London, Stephanie J.; Hall, Ian P.; Gudnason, Vilmundur; Tobin, Martin D.
In: Nature Genetics, Vol. 43, No. 11, 11.2011, p. 1082-1090.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function
AU - Artigas, María Soler
AU - Loth, Daan W.
AU - Wain, Louise V.
AU - Gharib, Sina A.
AU - Obeidat, Ma'En
AU - Tang, Wenbo
AU - Zhai, Guangju
AU - Zhao, Jing Hua
AU - Smith, Albert Vernon
AU - Huffman, Jennifer E.
AU - Albrecht, Eva
AU - Jackson, Catherine M.
AU - Evans, David M.
AU - Cadby, Gemma
AU - Fornage, Myriam
AU - Manichaikul, Ani
AU - Lopez, Lorna M.
AU - Johnson, Toby
AU - Aldrich, Melinda C.
AU - Aspelund, Thor
AU - Barroso, Ins
AU - Campbell, Harry
AU - Cassano, Patricia A.
AU - Couper, David J.
AU - Eiriksdottir, Gudny
AU - Franceschini, Nora
AU - Garcia, Melissa
AU - Gieger, Christian
AU - Gislason, Gauti Kjartan
AU - Grkovic, Ivica
AU - Hammond, Christopher J.
AU - Hancock, Dana B.
AU - Harris, Tamara B.
AU - Ramasamy, Adaikalavan
AU - Heckbert, Susan R.
AU - Heliövaara, Markku
AU - Homuth, Georg
AU - Hysi, Pirro G.
AU - James, Alan L.
AU - Jankovic, Stipan
AU - Joubert, Bonnie R.
AU - Karrasch, Stefan
AU - Klopp, Norman
AU - Koch, Beate
AU - Kritchevsky, Stephen B.
AU - Launer, Lenore J.
AU - Liu, Yongmei
AU - Loehr, Laura R.
AU - Lohman, Kurt
AU - Loos, Ruth J.F.
AU - Lumley, Thomas
AU - Al Balushi, Khalid A.
AU - Ang, Wei Q.
AU - Barr, R. Graham
AU - Beilby, John
AU - Blakey, John D.
AU - Boban, Mladen
AU - Boraska, Vesna
AU - Brisman, Jonas
AU - Britton, John R.
AU - Brusselle, Guy G.
AU - Cooper, Cyrus
AU - Curjuric, Ivan
AU - Dahgam, Santosh
AU - Deary, Ian J.
AU - Ebrahim, Shah
AU - Eijgelsheim, Mark
AU - Francks, Clyde
AU - Gaysina, Darya
AU - Granell, Raquel
AU - Gu, Xiangjun
AU - Hankinson, John L.
AU - Hardy, Rebecca
AU - Harris, Sarah E.
AU - Henderson, John
AU - Henry, Amanda
AU - Hingorani, Aroon D.
AU - Hofman, Albert
AU - Holt, Patrick G.
AU - Hui, Jennie
AU - Hunter, Michael L.
AU - Imboden, Medea
AU - Jameson, Karen A.
AU - Kerr, Shona M.
AU - Kolcic, Ivana
AU - Kronenberg, Florian
AU - Liu, Jason Z.
AU - Marchini, Jonathan
AU - McKeever, Tricia
AU - Morris, Andrew D.
AU - Olin, Anna Carin
AU - Porteous, David J.
AU - Postma, Dirkje S.
AU - Rich, Stephen S.
AU - Ring, Susan M.
AU - Rivadeneira, Fernando
AU - Rochat, Thierry
AU - Sayer, Avan Aihie
AU - Sayers, Ian
AU - Sly, Peter D.
AU - Smith, George Davey
AU - Sood, Akshay
AU - Starr, John M.
AU - Uitterlinden, André G.
AU - Vonk, Judith M.
AU - Wannamethee, S. Goya
AU - Whincup, Peter H.
AU - Wijmenga, Cisca
AU - Williams, O. Dale
AU - Wong, Andrew
AU - Mangino, Massimo
AU - Marciante, Kristin D.
AU - McArdle, Wendy L.
AU - Meibohm, Bernd
AU - Morrison, Alanna C.
AU - North, Kari E.
AU - Omenaas, Ernst
AU - Palmer, Lyle J.
AU - Pietiläinen, Kirsi H.
AU - Pin, Isabelle
AU - Polašek, Ozren
AU - Pouta, Anneli
AU - Psaty, Bruce M.
AU - Hartikainen, Anna Liisa
AU - Rantanen, Taina
AU - Ripatti, Samuli
AU - Rotter, Jerome I.
AU - Rudan, Igor
AU - Rudnicka, Alicja R.
AU - Schulz, Holger
AU - Shin, So Youn
AU - Spector, Tim D.
AU - Surakka, Ida
AU - Vitart, Veronique
AU - Völzke, Henry
AU - Wareham, Nicholas J.
AU - Warrington, Nicole M.
AU - Wichmann, H. Erich
AU - Wild, Sarah H.
AU - Wilk, Jemma B.
AU - Wjst, Matthias
AU - Wright, Alan F.
AU - Zgaga, Lina
AU - Zemunik, Tatijana
AU - Pennell, Craig E.
AU - Nyberg, Fredrik
AU - Kuh, Diana
AU - Holloway, John W.
AU - Boezen, H. Marike
AU - Lawlor, Debbie A.
AU - Morris, Richard W.
AU - Probst-Hensch, Nicole
AU - Kaprio, Jaakko
AU - Wilson, James F.
AU - Hayward, Caroline
AU - Kähönen, Mika
AU - Heinrich, Joachim
AU - Musk, Arthur W.
AU - Jarvis, Deborah L.
AU - Gläser, Sven
AU - Järvelin, Marjo Riitta
AU - Ch Stricker, Bruno H.
AU - Elliott, Paul
AU - O'Connor, George T.
AU - Strachan, David P.
AU - London, Stephanie J.
AU - Hall, Ian P.
AU - Gudnason, Vilmundur
AU - Tobin, Martin D.
N1 - Funding Information: We thank the many colleagues who contributed to collection and phenotypic characterization of the clinical sampling, genotyping and analysis of the data. We especially thank those who kindly agreed to participate in the studies. Major funding for this work is from the following sources (alphabetical): Academy of Finland (project grants 104781, 120315, 129269, 1114194, Center of Excellence in Complex Disease Genetics (213506 and 129680) and SALVE); Althingi (Icelandic Parliament); Arthritis Research Campaign; Asthma UK; AstraZeneca; AXA Research Fund; Biotechnology and Biological Sciences Research Council (BBSRC) (BB/F019394/1, G20234); British Heart Foundation (PG/97012, PG/06/154/22043, FS05/125); British Lung Foundation; Canadian Institutes of Health Research (Grant ID MOP-82893); Cancer Research United Kingdom; Funding Information: N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, N01-HC-45204, N01 HC-25195, N01-HC-95159 through N01-HC-95169, RR-024156, N02-HL-6-4278, R01 HL-071022, R01 HL-077612, R01 HL-074104, RC1 HL100543, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C, grants HL080295, HL087652, HL105756, R01-HL-084099, R01HL087641, R01HL59367, R01HL086694, HL088133, HL075336 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), 1K23HL094531-01); US NIH National Institute of Allergy and Infectious Diseases (NIAID); US NIH National Institute of Child Health and Human Development (NICHD); US NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK063491); US NIH National Institute of Environmental Health Sciences (NIEHS) (ZO1 ES49019, ES015794); US NIH National Institute of Mental Health (NIMH) (5R01MH63706:02); US NIH National Institute of Neurological Disorders and Stroke (NINDD); US NIH National Institute on Aging (NIA) (R01 AG032098, RC1 AG035835, N01AG12100, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1, AG-023269, AG-15928, AG-20098, AG-027058); Wellcome Trust (077016/Z/05/Z, GR069224, 068545/Z/02, 076113/B/04/Z, 079895). Funding Information: Chief Scientist Office, Scottish Government Health Directorate (CZD/16/6); Croatian Institute for Public Health; UK Department of Health; Dutch Kidney Foundation; Erasmus Medical Center and Erasmus University, Rotterdam; Estonian Genome Center, University of Tartu, Estonia (SF0180142s08); EU funding (GABRIEL GRANT Number: 018996, ECRHS II Coordination Number: QLK4-CT-1999-01237); European Commission (DG XII, EURO-BLCS, FP-5 QLG1-CT-2000-01643, FP-6 LSHB-CT-2006-018996 (GABRIEL), FP-6 LSHG-CT-2006-018947 (EUROSPAN), FP-6 GenomEUtwin project QLG2-CT-2002-01254, FP7/2007-2013: HEALTH-F2-2008-201865, GEFOS, HEALTH-F2-2008-35627, TREAT-OA, HEALTH-F4-2007-201413 (ENGAGE)); Finnish Foundation for Cardiovascular Research; Flight Attendant Medical Research Institute (FAMRI); German Asthma and COPD Network (COSYCONET: BMBF grant 01GI0883); German Bundesministerium fuer Forschung und Technology (01 AK 803 A-H, 01 IG 07015 G); German Federal Ministry of Education and Research (BMBF) (03ZIK012, 01ZZ9603, 01ZZ0103 and 01ZZ0403): German National Genome Research Network (NGFN-2 and NGFN-plus); German Ministry of Cultural Affairs; GlaxoSmithKline; Gyllenberg Foundations; Healthway, Western Australia; Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Healthcare and Bioscience iNet (funded by the East Midlands Development Agency, partially financed by the European Regional Development Fund, delivered by Medilink East Midlands); Higher Education Funding Council for England (HEFCE); Hjartavernd (Icelandic Heart Association); Innsbruck Medical University; Institute for Anthropological Research in Zagreb; International Osteoporosis Foundation; Intramural Research Program of the NIH, National Institute on Aging and National Institute of Environmental Health Sciences; Jalmari and Rauha Ahokas Foundation; Juvenile Diabetes Research Foundation International (JDRF); Lifelong Health and Wellbeing Initiative (G0700704/84698); Medical Research Council UK (G1000861, G0501942, G0902313, G0000934, G0800582, G0500539, G0600705, PrevMetSyn/SALVE, G9901462); Medical Research Fund of the Tampere University Hospital; Ministry of Science, Education and Sport of the Republic of Croatia (108-1080315-0302); Medical Research Council Human Genetics Unit; Medisearch–The Leicester Medical Research Foundation; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; National Health and Medical Research Council of Australia (Grant ID 403981 and ID 003209); National Human Genome Research Institute (NHGRI) (U01-HG-004729, U01-HG-004402); National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centres (Guy’s & St. Thomas’ NHS Foundation Trust in partnership with King’s College London and Cambridge University Hospitals NHS Foundation Trust in partnership with the University of Cambridge); Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) (050-060-810); Netherlands Organization for the Health Research and Development (ZonMw); Netherlands Organization of Scientific Research NOW (1750102007006, 175.010.2005.011, 911-03-012); Northern Netherlands Collaboration of Provinces (SNN); Norwegian University of Science and Technology; Novo Nordisk; Ontario Institute of Cancer Research and Canadian Cancer Society Research Institute (CCSRI 020214); Republic of Croatia Ministry of Science, Education and Sports research grants (108-1080315-0302); Research Institute for Diseases in the Elderly (RIDE) (014-93-015: RIDE2); Research Into Ageing (251); Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg–West Pomerania; Social Ministry of the Federal State of Mecklenburg–West Pomerania; Structure Enhancing Fund (FES) of the Dutch government; Swedish Heart and Lung Foundation grant 20050561; Swedish Research Council for Worklife and Social research (FAS), grants 2001-0263, 2003-0139; Swiss National Science Foundation (grants no. 4026-28099,3347CO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 32-65896.01,32-59302.99, 32-52720.97, 32-4253.94); The Asthma, Allergy and Inflammation Research Trust; The Great Wine Estates of the Margaret River region of Western Australia; The Netherlands’ Ministry of Economic Affairs, Ministry of Education, Culture and Science and Ministry for Health, Welfare and Sports; The Royal Society; The University of Split and Zagreb Medical Schools; Tromsø University; U01 DK062418; UBS Wealth Foundation Grant BA29s8Q7-DZZ; UK Department of Health Policy Research Programme; University Hospital Oulu, Biocenter, University of Oulu, Finland (75617); University Medical Center Groningen; University of Bristol; University of Leicester HEFCE CIF award; University of Nottingham; US National Institutes of Health (NIH) (1P50 CA70907, RO1 CA121197, U19 CA148127, CA55769, CA127219, R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259, UL1RR025005, contracts HHSN268200625226C, HHSN268200782096C, R01-HL084099); US NIH National Cancer Institute (RO1CA111703); US NIH National Center for Research Resources (grants M01-RR00425 and 5M01 RR00997); US NIH National Eye Institute (NEI); US NIH National Heart, Lung and Blood Institute (contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049,
PY - 2011/11
Y1 - 2011/11
N2 - 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 ×-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.
AB - 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 ×-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.
UR - http://www.scopus.com/inward/record.url?scp=80055008094&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80055008094&partnerID=8YFLogxK
U2 - 10.1038/ng.941
DO - 10.1038/ng.941
M3 - Article
C2 - 21946350
AN - SCOPUS:80055008094
VL - 43
SP - 1082
EP - 1090
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 11
ER -