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

Daan W. Loth, María Soler Artigas, Sina A. Gharib, 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 TrochetMika 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

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Abstract

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.

Original languageEnglish
Pages (from-to)669-677
Number of pages9
JournalNature Genetics
Volume46
Issue number7
DOIs
StatePublished - Jul 2014

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    Loth, D. W., Artigas, M. S., Gharib, S. A., Wain, L. V., Franceschini, N., Koch, B., Pottinger, T. D., Smith, A. V., Duan, Q., Oldmeadow, C., Lee, M. K., Strachan, D. P., James, A. L., Huffman, J. E., Vitart, V., Ramasamy, A., Wareham, N. J., Kaprio, J., Wang, X. Q., ... London, S. J. (2014). Genome-wide association analysis identifies six new loci associated with forced vital capacity. Nature Genetics, 46(7), 669-677. https://doi.org/10.1038/ng.3011