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

Loth, Daan W. and Artigas, María Soler and Gharib, Sina A. and Wain, Louise V. and Franceschini, Nora and Koch, Beate and Pottinger, Tess D. and Smith, Albert Vernon and Duan, Qing and Oldmeadow, Chris and Lee, Mi Kyeong and Strachan, David P. and James, Alan L. and Huffman, Jennifer E. and Vitart, Veronique and Ramasamy, Adaikalavan and Wareham, Nicholas J. and Kaprio, Jaakko and Wang, Xin-Qun and Trochet, Holly and Kähönen, Mika and Flexeder, Claudia and Albrecht, Eva and Lopez, Lorna M. and de Jong, Kim and Thyagarajan, Bharat and Alves, Alexessander Couto and Enroth, Stefan and Omenaas, Ernst and Joshi, Peter K. and Fall, Tove and Viñuela, Ana and Launer, Lenore J. and Loehr, Laura R. and Fornage, Myriam and Li, Guo and Wilk, Jemma B. and Tang, Wenbo and Manichaikul, Ani and Lahousse, Lies and Harris, Tamara B. and North, Kari E. and Rudnicka, Alicja R. and Hui, Jennie and Gu, Xiangjun and Lumley, Thomas and Wright, Alan F. and Hastie, Nicholas D. and Campbell, Susan and Kumar, Rajesh and Pin, Isabelle and Scott, Robert A. and Pietiläinen, Kirsi H. and Surakka, Ida and Liu, Yongmei and Holliday, Elizabeth G. and Schulz, Holger and Heinrich, Joachim and Davies, Gail and Vonk, Judith M. and Wojczynski, Mary and Pouta, Anneli and Johansson, Åsa and Wild, Sarah H. and Ingelsson, Erik and Rivadeneira, Fernando and Völzke, Henry and Hysi, Pirro G. and Eiriksdottir, Gudny and Morrison, Alanna C. and Rotter, Jerome I. and Gao, Wei and Postma, Dirkje S. and White, Wendy B. and Rich, Stephen S. and Hofman, Albert and Aspelund, Thor and Couper, David and Smith, Lewis J. and Psaty, Bruce M. and Lohman, Kurt and Burchard, Esteban G. and Uitterlinden, André G. and Garcia, Melissa and Joubert, Bonnie R. and McArdle, Wendy L. and Musk, A Bill and Hansel, Nadia and Heckbert, Susan R. and Zgaga, Lina and van Meurs, Joyce B.J. and Navarro, Pau and Rudan, Igor and Oh, Yeon-Mok and Redline, Susan and Jarvis, Deborah L. and Zhao, Jing Hua and Rantanen, Taina and O'Connor, George T. and Ripatti, Samuli and Scott, Rodney J. and Karrasch, Stefan and Grallert, Harald and Gaddis, Nathan C. and Starr, John M. and Wijmenga, Cisca and Minster, Ryan L. and Lederer, David J. and Pekkanen, Juha and Gyllensten, Ulf and Campbell, Harry and Morris, Andrew P. and Gläser, Sven and Hammond, Christopher J. and Burkart, Kristin M and Beilby, John and Kritchevsky, Stephen B. and Gudnason, Vilmundur and Hancock, Dana B. and Williams, O Dale and Polasek, Ozren and Zemunik, Tatijana and Kolcic, Ivana and Petrini, Marcy F. and Wjst, Matthias and Kim, Woo Jin and Porteous, David J. and Smith, Blair H. and Viljanen, Anne and Heliövaara, Markku and Attia, John R. and Sayers, Ian and Hampel, Regina and Gieger, Christian and Deary, Ian J and Boezen, H. Marike and Newman, Anne and Jarvelin, Marjo-Riitta and Wilson, James F and Lind, Lars and Stricker, Bruno H. and Teumer, Alexander and Spector, Timothy D. and Melén, Erik and Peters, Marjolein J. and Lange, Leslie A. and Barr, R. Graham and Bracke, Ken R. and Verhamme, Fien M. and Sung, Joohon and Hiemstra, Pieter S. and Cassano, Patricia A. and Sood, Akshay and Hayward, Caroline and Dupuis, Josée and Hall, Ian P. and Brusselle, Guy G. and Tobin, Martin D. and London, Stephanie J. (2014) Genome-wide association analysis identifies six new loci associated with forced vital capacity. Nature Genetics, 46 (7). pp. 669-677. ISSN 1546-1718

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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.

Item Type: Article
Keywords: Genetics research, Genome-wide association studies, Population genetics, Respiratory tract diseases
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Medicine > Division of Respiratory Medicine
Identification Number: https://doi.org/10.1038/ng.3011
Depositing User: Eprints, Support
Date Deposited: 05 Apr 2016 10:00
Last Modified: 15 Sep 2016 20:51
URI: http://eprints.nottingham.ac.uk/id/eprint/32637

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