Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk.
Xuemei JiYohan BosseMaria Teresa LandiJiang GuiXiangjun XiaoDavid QianPhilippe JoubertMaxime LamontagneYafang LiIvan GorlovMariella de BiasiYounghun HanOlga GorlovaRayjean J HungXifeng WuJames McKayXuchen ZongRobert Carreras-TorresDavid C ChristianiNeil CaporasoMattias JohanssonGeoffrey LiuStig Egil BojesenLoic Le MarchandDemetrios AlbanesHeike BickeböllerMelinda C AldrichWilliam S BushAdonina TardonGadi RennertChu ChenM Dawn TeareJohn K FieldLambertus A KiemeneyPhilip LazarusAage HaugenStephen LamMatthew B SchabathAngeline S AndrewHongbing ShenYun-Chul HongJian-Min YuanPier Alberto BertazziAngela Cecilia PesatoriYuanqing YeNancy DiaoLi SuRuyang ZhangYonathan BrhaneNatasha LeighlJakob S JohansenAnders MellemgaardWalid SalibaChristopher HaimanLynne WilkensAna Fernandez-SomoanoGuillermo Fernandez-TardonErik H F M van der HeijdenJin Hee KimJuncheng DaiZhibin HuMichael P A DaviesMichael W MarcusHans BrunnströmJonas ManjerOlle MelanderDavid C MullerKim OvervadAntonia TrichopoulouRosario TuminoJennifer DohertyGary E GoodmanAngela CoxFiona TaylorPenella WollIrene BrüskeJudith ManzThomas MuleyAngela RischAlbert RosenbergerKjell GrankvistMikael JohanssonFrances ShepherdMing-Sound TsaoSusanne M ArnoldEric B HauraCiprian BolcaIvana HolcatovaVladimir JanoutMilica KonticJolanta LissowskaAnush MukeriaSimona OgnjanovicTadeusz M OrlowskiGhislaine SceloBeata SwiatkowskaDavid ZaridzePer BakkeVidar SkaugShanbeh ZienolddinyEric J DuellLesley M ButlerWoon-Puay KohYu-Tang GaoRichard S HoulstonJohn McLaughlinVictoria StevensDavid C NickleMa'en ObeidatHidde J HaismaBin ZhuLei SongMaría Soler ArtigasMartin D TobinLouise V WainFangyi GuJinyoung ByunAhsan KamalDakai ZhuRachel F TyndaleWei-Qi WeiStephen ChanockPaul J BrennanChristopher Ian AmosPublished in: Nature communications (2018)
Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.