6533b857fe1ef96bd12b461f
RESEARCH PRODUCT
Meta-analysis of exome array data identifies six novel genetic loci for lung function
Oluf PedersonKristin M. BurkartKonstantin StrauchJohanne Marie JustesenAlbert V. SmithMegan L. GroveGail DaviesJennifer A. BrodyNora FranceschiniMedea ImbodenMedea ImbodenAnu LoukolaAndrew P. MorrisAndrew P. MorrisSusan R. HeckbertJennifer E. HuffmanYongmei LiuJohn M. StarrStefan WeissKurt LohmanHenrik VestergaardHenrik VestergaardBlair H. SmithOzren PolasekAnubha MahajanArchie CampbellKari E. NorthMika KähönenGuy BrusselleGuy BrusselleNicole Probst-henschNicole Probst-henschAni ManichaikulTess D. PottingerTess D. PottingerAndré G. UitterlindenCharlotta PisingerStephen S. RichTraci M. BartzVilmundur GudnasonGeorge T. O'connorR. Graham BarrErik IngelssonErik IngelssonStefan EnrothBruce M. PsatyBruce M. PsatyLars LindWei GaoTamara B. HarrisDon D. SinPatricia A. CassanoSven GläserTerho LehtimäkiNiels GrarupJette Bork-jensenRuifang Li-gaoAnnah B. WyssÅSa JohanssonJin LiYohan BosséMa'en ObeidatJeanne C. LatourelleJosée DupuisIan J. DearyJames G. WilsonBeenish QaiserDennis O. Mook-kanamoriTaina RantanenAshok KumarStephen B. KritchevskyBram PrinsCaroline HaywardStefan KarraschTea SkaabyTarunveer S. AhluwaliaTarunveer S. AhluwaliaAlexander TeumerUlf GyllenstenLies LahousseLies LahousseVictoria E. JacksonEleftheria ZegginiWim TimensKent D. TaylorAllan LinnebergAllan LinnebergJonathan MartenOlli T. RaitakariOlli T. RaitakariTobias BontenSarah E. HarrisElisabeth AltmaierDavid J. PorteousTorben HansenWenbo TangWenbo TangIan P. HallSina A. GharibLouise V. WainLouise V. WainRenée De MutsertShona M. KerrRajesh RawalKe HaoBeate StubbeColleen M. SitlaniJosyf C. MychaleckyjLeslie A. LangeAldi T. KrajaDavid P. StrachanMartin D. TobinMartin D. TobinLeo-pekka LyytikäinenGudny EiriksdottirM. Arfan IkramAllan Lind-thomsenMichael A. ProvinceStephanie J. LondonAlanna C. MorrisonHolger SchulzJaakko KaprioJaakko Kapriosubject
0301 basic medicineNonsynonymous substitutionVital capacityMedicine (miscellaneous)Genome-wide association studySingle-nucleotide polymorphismBiologyGenomeGeneral Biochemistry Genetics and Molecular Biologyhengityselimet03 medical and health sciencesFEV1/FVC ratio0302 clinical medicineMedicine and Health SciencesmedicineCOPDGWASkeuhkotExome030304 developmental biologyGenetics0303 health sciencesCOPDexome arrayta1184Lung function respiratory exome array GWAS COPDBiology and Life Sciencesta3141lung functionArticlesGenomicsta3121respiratory systemrespiratorymedicine.diseaserespiratory tract diseases030104 developmental biology030220 oncology & carcinogenesisExpression quantitative trait lociResearch Articledescription
Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-08-07 |