Meta-analysis of exome array data identifies six novel genetic loci for lung function.
Victoria E JacksonJeanne C LatourelleLouise V WainAlbert V SmithMegan L GroveTraci M BartzMa'en ObeidatMichael A ProvinceWei GaoBeenish QaiserDavid J PorteousPatricia A CassanoTarunveer Singh AhluwaliaNiels GrarupJin LiElisabeth AltmaierJonathan MartenSarah E HarrisAni ManichaikulTess D PottingerRuifang Li-GaoAllan Lind-ThomsenAnubha MahajanLies LahousseMedea ImbodenAlexander TeumerBram PrinsLeo-Pekka LyytikainenGudny EiriksdottirNora FranceschiniColleen M SitlaniJennifer A BrodyYohan BosseHidde J HaismaAldi KrajaAnu LoukolaWenbo TangYongmei LiuJette Bork-JensenJohanne Marie JustesenAllan LinnebergLeslie A LangeRajesh RawalStefan KarraschJennifer E HuffmanBlair Hamilton SmithGail DaviesKristin M BurkartJosyf C MychaleckyiTobias N BontenStefan EnrothLars LindGuy G BrusselleAshish KumarBeate Stubbenull nullMika KähönenAnnah B WyssBruce M PsatySusan R HeckbertKe HaoTaina RantanenStephen B KritchevskyKurt LohmanTea SkaabyCharlotta PisingerTorben HansenHolger SchulzOzren PolasekArchie I CampbellJohn M StarrStephen S RichDennis O Mook-KanamoriÅsa JohanssonErik IngelssonAndré G UitterlindenStefan WeissOlli T RaitakariVilmundur GudnasonKari E NorthSina A GharibDon D SinKent D TaylorGeorge T O'ConnorJaakko A KaprioTamara B HarrisOluf PedersonHenrik VestergaardJames G WilsonKonstantin StrauchCaroline HaywardShona M KerrIan J DearyR Graham BarrRenée de MutsertUlf GyllenstenAndrew P MorrisM Arfan IkramNicole Probst-HenschSven GläserEleftheria ZegginiTerho LehtimäkiDavid P StrachanJosée DupuisAlanna C MorrisonIan P HallMartin D TobinStephanie J LondonPublished in: Wellcome open research (2018)
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 (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/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.
Keyphrases
- lung function
- genome wide
- dna methylation
- meta analyses
- copy number
- systematic review
- cystic fibrosis
- chronic obstructive pulmonary disease
- gene expression
- air pollution
- case control
- high resolution
- high throughput
- electronic health record
- genome wide association study
- randomized controlled trial
- poor prognosis
- big data
- pulmonary hypertension
- genome wide association
- data analysis
- binding protein
- mass spectrometry
- deep learning
- artificial intelligence