6533b821fe1ef96bd127bbaa

RESEARCH PRODUCT

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

Repapi ESayers IWain LvBurton RbJohnson TObeidat MZhao JhRamasamy AZhai GVitart VHuffman JeIgl WAlbrecht EDeloukas PHenderson JGranell JMcardle WlRudnicka ArWellcome Trust Case Control ConsortiumBarroso ILoos RjfWareham NjMustelin LTaina RantanenSurakka IImboden MWichmann HeGrkovic IJankovic SZgaga LHartikainen APeltonen LGyllensten UJohansson ÅZaboli GCampbell HWild ShWilson JfGläser SHomuth GVölzke HMangino MSoranzo NSpector TdPolašek ORudan IWright AfHeliövaara MRipatti SPouta ATorinsson Naluai ÅOlin ATorén KCooper MnJames AlPalmer LjHingorani AdWannamethee SgWhincup PhSmith GdEbrahim SMckeever TmPavord IdMacleod AkMorris AdPorteous DjCooper CDennison EShaheen SKarrasch SSchnabel ESchulz HGrallert HBouatia-naji NDelplanque JFroguel PBlakey JdThe Nshd Respiratory Study TeamBritton JrMorris RwHolloway JwLawlor DaHui JNyberg FJarvelin MJackson CKähönen MKaprio JProbst-hensch NmKoch BHayward CEvans DeElliott PStrachan DpHall IpTobin Md

subject

geenitkeuhkotoiminnotrespiratory systemgeneticLung function

description

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 (FEV1) and the ratio of FEV1 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 ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 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. peerReviewed

yearjournalcountryeditionlanguage
2010-01-01
http://urn.fi/URN:NBN:fi:jyu-201909184206