Login / Signup

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Jianxin ShiKouya ShiraishiJiyeon ChoiKeitaro MatsuoTzu-Yu ChenJuncheng DaiRayjean J HungKexin ChenXiao-Ou ShuYoung Tae KimMaria Teresa LandiDongxin LinQuan LongZhihua YinBao Sen ZhouBao SongJiucun WangWei Jie SeowLei SongI-Shou ChangWei HuLi-Hsin ChienQiuyin CaiYun-Chul HongHee Nam KimYi-Long WuMaria Pik WongBrian Douglas RichardsonKaren M FunderburkShilan LiTongwu ZhangCharles BreezeZhaoming WangBatel BlechterBryan A BassigJin Hee KimDemetrios AlbanesJason Y Y WongMin-Ho ShinLap Ping ChungYang YangShe-Juan AnHong ZhengYasushi YatabeXu Chao ZhangYoung-Chul KimNeil E CaporasoJiang ChangChung Man James HoMichiaki KuboYataro DaigoMinsun SongYukihide MomozawaYoichiro KamataniMasashi KobayashiKenichi OkuboTakayuki HondaDean H HosgoodHideo KunitohHarsh PatelShun-Ichi WatanabeYohei MiyagiHaruhiko NakayamaShingo MatsumotoHidehito HorinouchiMasahiro TsuboiRyuji HamamotoKoichi GotoYuichiro OheAtsushi TakahashiAkiteru GotoYoshihiro MinamiyaMegumi HaraYuichiro NishidaKenji TakeuchiKenji WakaiKoichi MatsudaYoshinori MurakamiKimihiro ShimizuHiroyuki SuzukiKatsuharu SaitoYoichi OhtakiKazumi TanakaTangchun WuFusheng WeiHongji DaiMitchell J MachielaJian SuYeul Hong KimIn Jae OhVictor Ho Fun LeeGee-Chen ChangYing-Huang TsaiKuan-Yu ChenMing-Shyan HuangWu-Chou SuYuh-Min ChenAdeline SeowJae Yong ParkSun-Seog KweonKun-Chieh ChenYu-Tang GaoBiyun QianChen WuDaru LuJian-Jun LiuAnn G SchwartzRichard S HoulstonMargaret R SpitzIvan P GorlovXifeng WuPing YangStephen LamAdonina TardónChu ChenStig Egil BojesenMattias J JohanssonAngela RischHeike BickeböllerBu-Tian JiH-Erich WichmannDavid Chistopher ChristianiGadi RennertSusanne M ArnoldPaul BrennanJames McKayJohn K FieldSanjay S SheteLoic Le MarchandGeoffrey LiuAngeline AndrewLambertus A L M KiemeneyShan Zienolddiny-NaruiKjell GrankvistMikael JohanssonAngela CoxFiona TaylorWoon-Puay KohPhilip LazarusMatthew B SchabathMelinda C AldrichHyo-Sung JeonShih Sheng JiangJae Sook SungChung-Hsing ChenChin-Fu HsiaoYoo Jin JungHuan GuoZhi-Bin HuLaurie BurdettMeredith YeagerAmy HutchinsonBelynda D HicksJia LiuBin ZhuSonja I BerndtWei WuJunwen WangYuqing LiJin Eun ChoiKyong Hwa ParkSook Whan SungLi LiuChang Hyun KangWen-Chang WangJun XuPeng GuanWen TanChong-Jen YuGong YangAlan Dart Loon SihoeYing ChenYi Young ChoiJun Suk KimHo-Il YoonIn Kyu ParkPing XuQincheng HeChih-Liang WangHsiao-Han HungRoel C H VermeulenIona ChengJunjie WuWei-Yen LimFang-Yu TsaiJohn K C ChanJihua LiHongyan ChenHsien-Chih LinLi JinJie LiuNorie SawadaTaiki YamajiKathleen WyattShengchao A LiHongxia MaMeng ZhuZhehai WangSensen ChengXuelian LiYangwu RenAnn ChaoMotoki IwasakiJunjie ZhuGening JiangKe FeiGuoping WuChih-Yi ChenChien-Jen ChenPan-Chyr YangJinming YuVictoria L StevensJoseph F FraumeniNilanjan ChatterjeeOlga Y GorlovaChao Agnes HsiungChristopher Ian AmosHongbing ShenStephen J ChanockNathaniel RothmanTakashi KohnoQing Lan
Published in: Nature communications (2023)
Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.
Keyphrases