Genome-wide association analysis identifies six new loci associated with forced vital capacity.

Authors:
Sina A Gharib, MD
Sina A Gharib, MD
Center for Lung Biology, UW Medicine Sleep Center, University of Washington
Associate Professor
Seattle, WA | United States
Daan W Loth María Soler Artigas Louise V Wain Nora Franceschini Beate Koch Tess D Pottinger Albert Vernon Smith Qing Duan Chris Oldmeadow Mi Kyeong Lee David P Strachan Alan L James Jennifer E Huffman Veronique Vitart Adaikalavan Ramasamy Nicholas J Wareham Jaakko Kaprio Xin-Qun Wang Holly Trochet Mika Kähönen Claudia Flexeder Eva Albrecht Lorna M Lopez Kim de Jong Bharat Thyagarajan Alexessander Couto Alves Stefan Enroth Ernst Omenaas Peter K Joshi Tove Fall Ana Viñuela Lenore J Launer Laura R Loehr Myriam Fornage Guo Li Jemma B Wilk Wenbo Tang Ani Manichaikul Lies Lahousse Tamara B Harris Kari E North Alicja R Rudnicka Jennie Hui Xiangjun Gu Thomas Lumley Alan F Wright Nicholas D Hastie Susan Campbell Rajesh Kumar Isabelle Pin Robert A Scott Kirsi H Pietiläinen Ida Surakka Yongmei Liu Elizabeth G Holliday Holger Schulz Joachim Heinrich Gail Davies Judith M Vonk Mary Wojczynski Anneli Pouta Asa Johansson Sarah H Wild Erik Ingelsson Fernando Rivadeneira Henry Völzke Pirro G Hysi Gudny Eiriksdottir Alanna C Morrison Jerome I Rotter Wei Gao Dirkje S Postma Wendy B White Stephen S Rich Albert Hofman Thor Aspelund David Couper Lewis J Smith Bruce M Psaty Kurt Lohman Esteban G Burchard André G Uitterlinden Melissa Garcia Bonnie R Joubert Wendy L McArdle A Bill Musk Nadia Hansel Susan R Heckbert Lina Zgaga Joyce B J van Meurs Pau Navarro Igor Rudan Yeon-Mok Oh Susan Redline Deborah L Jarvis Jing Hua Zhao Taina Rantanen George T O'Connor Samuli Ripatti Rodney J Scott Stefan Karrasch Harald Grallert Nathan C Gaddis John M Starr Cisca Wijmenga Ryan L Minster David J Lederer Juha Pekkanen Ulf Gyllensten Harry Campbell Andrew P Morris Sven Gläser Christopher J Hammond Kristin M Burkart John Beilby Stephen B Kritchevsky Vilmundur Gudnason Dana B Hancock O Dale Williams Ozren Polasek Tatijana Zemunik Ivana Kolcic Marcy F Petrini Matthias Wjst Woo Jin Kim David J Porteous Generation Scotland Blair H Smith Anne Viljanen Markku Heliövaara John R Attia Ian Sayers Regina Hampel Christian Gieger Ian J Deary H Marike Boezen Anne Newman Marjo-Riitta Jarvelin James F Wilson Lars Lind Bruno H Stricker Alexander Teumer Timothy D Spector Erik Melén Marjolein J Peters Leslie A Lange R Graham Barr Ken R Bracke Fien M Verhamme Joohon Sung Pieter S Hiemstra Patricia A Cassano Akshay Sood Caroline Hayward Josée Dupuis Ian P Hall Guy G Brusselle Martin D Tobin Stephanie J London

Nat Genet 2014 Jul 15;46(7):669-77. Epub 2014 Jun 15.

1] Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, US Department of Health and Human Services, Research Triangle Park, North Carolina, USA. [2].

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

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July 2014
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