Title | Genome-wide association analysis identifies six new loci associated with forced vital capacity. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Loth, DW, Artigas, MSoler, Gharib, SA, Wain, LV, Franceschini, N, Koch, B, Pottinger, TD, Smith, AVernon, Duan, Q, Oldmeadow, C, Lee, MKyeong, Strachan, DP, James, AL, Huffman, JE, Vitart, V, Ramasamy, A, Wareham, NJ, Kaprio, J, Wang, X-Q, Trochet, H, Kähönen, M, Flexeder, C, Albrecht, E, Lopez, LM, de Jong, K, Thyagarajan, B, Alves, ACouto, Enroth, S, Omenaas, E, Joshi, PK, Fall, T, Viñuela, A, Launer, LJ, Loehr, LR, Fornage, M, Li, G, Wilk, JB, Tang, W, Manichaikul, A, Lahousse, L, Harris, TB, North, KE, Rudnicka, AR, Hui, J, Gu, X, Lumley, T, Wright, AF, Hastie, ND, Campbell, S, Kumar, R, Pin, I, Scott, RA, Pietiläinen, KH, Surakka, I, Liu, Y, Holliday, EG, Schulz, H, Heinrich, J, Davies, G, Vonk, JM, Wojczynski, M, Pouta, A, Johansson, A, Wild, SH, Ingelsson, E, Rivadeneira, F, Völzke, H, Hysi, PG, Eiriksdottir, G, Morrison, AC, Rotter, JI, Gao, W, Postma, DS, White, WB, Rich, SS, Hofman, A, Aspelund, T, Couper, D, Smith, LJ, Psaty, BM, Lohman, K, Burchard, EG, Uitterlinden, AG, Garcia, M, Joubert, BR, McArdle, WL, A Musk, B, Hansel, N, Heckbert, SR, Zgaga, L, van Meurs, JBJ, Navarro, P, Rudan, I, Oh, Y-M, Redline, S, Jarvis, DL, Zhao, JH, Rantanen, T, O'Connor, GT, Ripatti, S, Scott, RJ, Karrasch, S, Grallert, H, Gaddis, NC, Starr, JM, Wijmenga, C, Minster, RL, Lederer, DJ, Pekkanen, J, Gyllensten, U, Campbell, H, Morris, AP, Gläser, S, Hammond, CJ, Burkart, KM, Beilby, J, Kritchevsky, SB, Gudnason, V, Hancock, DB, O Williams, D, Polasek, O, Zemunik, T, Kolcic, I, Petrini, MF, Wjst, M, Kim, WJin, Porteous, DJ, Scotland, G, Smith, BH, Viljanen, A, Heliövaara, M, Attia, JR, Sayers, I, Hampel, R, Gieger, C, Deary, IJ, H Boezen, M, Newman, A, Jarvelin, M-R, Wilson, JF, Lind, L, Stricker, BH, Teumer, A, Spector, TD, Melén, E, Peters, MJ, Lange, LA, R Barr, G, Bracke, KR, Verhamme, FM, Sung, J, Hiemstra, PS, Cassano, PA, Sood, A, Hayward, C, Dupuis, J, Hall, IP, Brusselle, GG, Tobin, MD, London, SJ |
Journal | Nat Genet |
Volume | 46 |
Issue | 7 |
Pagination | 669-77 |
Date Published | 2014 Jul |
ISSN | 1546-1718 |
Keywords | Cohort Studies, Databases, Genetic, Follow-Up Studies, Forced Expiratory Volume, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Lung Diseases, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Prognosis, Quantitative Trait Loci, Respiratory Function Tests, Spirometry, Vital Capacity |
Abstract | <p>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. </p> |
DOI | 10.1038/ng.3011 |
Alternate Journal | Nat. Genet. |
PubMed ID | 24929828 |
PubMed Central ID | PMC4140093 |
Grant List | ETM/55 / / Chief Scientist Office / United Kingdom CZB/4/505 / / Chief Scientist Office / United Kingdom CZB/4/710 / / Chief Scientist Office / United Kingdom G0100266 / / Medical Research Council / United Kingdom UL1 TR001079 / TR / NCATS NIH HHS / United States R25 MH083620 / MH / NIMH NIH HHS / United States R01 HL077612 / HL / NHLBI NIH HHS / United States G1000861 / / Medical Research Council / United Kingdom MR/L016400/1 / / Medical Research Council / United Kingdom UL1 TR000124 / TR / NCATS NIH HHS / United States MR/K026992/1 / / Medical Research Council / United Kingdom MC_UU_12015/1 / / Medical Research Council / United Kingdom R01 HL105756 / HL / NHLBI NIH HHS / United States MC_U106179471 / / Medical Research Council / United Kingdom P30 DK063491 / DK / NIDDK NIH HHS / United States U01 AG023749 / AG / NIA NIH HHS / United States MC_PC_U127592696 / / Medical Research Council / United Kingdom G0701863 / / Medical Research Council / United Kingdom CZD/16/6/4 / / Chief Scientist Office / United Kingdom MC_PC_U127561128 / / Medical Research Council / United Kingdom G0902313 / / Medical Research Council / United Kingdom U01 AG023746 / AG / NIA NIH HHS / United States G0700704 / / Medical Research Council / United Kingdom BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom Z01 ES043012-10 / / Intramural NIH HHS / United States R01 HL103676 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States SRF/01/010 / / Department of Health / United Kingdom N01 HC095159 / HC / NHLBI NIH HHS / United States |