Genome-wide association study identifies five loci associated with lung function.

TitleGenome-wide association study identifies five loci associated with lung function.
Publication TypeJournal Article
Year of Publication2010
AuthorsRepapi E, Sayers I, Wain LV, Burton PR, Johnson T, Obeidat M'en, Zhao J H, Ramasamy A, Zhai G, Vitart V, Huffman JE, Igl W, Albrecht E, Deloukas P, Henderson J, Granell R, McArdle WL, Rudnicka AR, Barroso I, Loos RJF, Wareham NJ, Mustelin L, Rantanen T, Surakka I, Imboden M, H Wichmann E, Grkovic I, Jankovic S, Zgaga L, Hartikainen A-L, Peltonen L, Gyllensten U, Johansson Å, Zaboli G, Campbell H, Wild SH, Wilson JF, Gläser S, Homuth G, Völzke H, Mangino M, Soranzo N, Spector TD, Polasek O, Rudan I, Wright AF, Heliövaara M, Ripatti S, Pouta A, Naluai ATorinsson, Olin A-C, Toren K, Cooper MN, James AL, Palmer LJ, Hingorani AD, Wannamethee GS, Whincup PH, Smith G D, Ebrahim S, McKeever TM, Pavord ID, MacLeod AK, Morris AD, Porteous DJ, Cooper C, Dennison E, Shaheen S, Karrasch S, Schnabel E, Schulz H, Grallert H, Bouatia-Naji N, Delplanque J, Froguel P, Blakey JD, Britton JR, Morris RW, Holloway JW, Lawlor DA, Hui J, Nyberg F, Jarvelin M-R, Jackson C, Kähönen M, Kaprio J, Probst-Hensch NM, Koch B, Hayward C, Evans DM, Elliott P, Strachan DP, Hall IP, Tobin MD
Corporate AuthorsWellcome Trust Case Control Consortium, NSHD Respiratory Study Team
JournalNat Genet
Volume42
Issue1
Pagination36-44
Date Published2010 Jan
ISSN1546-1718
KeywordsFemale, Forced Expiratory Volume, Gene Expression Profiling, Genome, Human, Genome-Wide Association Study, Glutathione Transferase, Humans, Lung, Male, Meta-Analysis as Topic, Microfilament Proteins, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Receptors, Immunologic, Receptors, Serotonin, 5-HT4, Respiratory Function Tests, RNA, Messenger, Spirometry, Thrombospondins, Vital Capacity
Abstract

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

DOI10.1038/ng.501
Alternate JournalNat. Genet.
PubMed ID20010834
PubMed Central IDPMC2862965
Grant List0020029 / / Department of Health / United Kingdom
068545/Z/02 / / Wellcome Trust / United Kingdom
075883 / / Wellcome Trust / United Kingdom
075883 / / Wellcome Trust / United Kingdom
076113/B/04/Z / / Wellcome Trust / United Kingdom
077016/Z/05/Z / / Wellcome Trust / United Kingdom
079895 / / Wellcome Trust / United Kingdom
086160/Z/08/A / / Wellcome Trust / United Kingdom
1RL1MH083268-01 / MH / NIMH NIH HHS / United States
5R01HL087679-02 / HL / NHLBI NIH HHS / United States
5R01MH63706:02 / MH / NIMH NIH HHS / United States
CZB/4/710 / / Chief Scientist Office / United Kingdom
CZD/16/6/2 / / Chief Scientist Office / United Kingdom
CZD/16/6/4 / / Chief Scientist Office / United Kingdom
G0000934 / / Medical Research Council / United Kingdom
G0000943 / / Medical Research Council / United Kingdom
G0401540 / / Medical Research Council / United Kingdom
G0500539 / / Medical Research Council / United Kingdom
G0501942 / / Medical Research Council / United Kingdom
G0600331 / / Medical Research Council / United Kingdom
G0600705 / / Medical Research Council / United Kingdom
G0800582 / / Medical Research Council / United Kingdom
G0801056 / / Medical Research Council / United Kingdom
G0902125 / / Medical Research Council / United Kingdom
G9815508 / / Medical Research Council / United Kingdom
G990146 / / Medical Research Council / United Kingdom
MC_U106179471 / / Medical Research Council / United Kingdom
MC_U106188470 / / Medical Research Council / United Kingdom
MC_U123092720 / / Medical Research Council / United Kingdom
MC_U123092721 / / Medical Research Council / United Kingdom
MC_U127561128 / / Medical Research Council / United Kingdom
MC_UP_A620_1014 / / Medical Research Council / United Kingdom
PG/06/154/22043 / / British Heart Foundation / United Kingdom
PG/97012 / / British Heart Foundation / United Kingdom
RG/08/013/25942 / / British Heart Foundation / United Kingdom
U.1230.00.008.00005.02 / / Medical Research Council / United Kingdom
U01 DK062418 / DK / NIDDK NIH HHS / United States
/ / Biotechnology and Biological Sciences Research Council / United Kingdom
/ / Chief Scientist Office / United Kingdom
/ / Cancer Research UK / United Kingdom