Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference

Meng, XiangruiXiangruiMengNavoly, GeorginaGeorginaNavolyGiannakopoulou, OlgaOlgaGiannakopoulouLevey, Daniel FDaniel FLeveyKoller, DoraDoraKollerPathak, Gita AGita APathakKoen, NastassjaNastassjaKoenLin, KuangKuangLinAdams, Mark JMark JAdamsRentería, Miguel EMiguel ERenteríaFeng, YanzheYanzheFengGaziano, J MichaelJ MichaelGazianoStein, Dan JDan JSteinZar, Heather JHeather JZarCampbell, Megan LMegan LCampbellvan Heel, David ADavid Avan HeelTrivedi, BhaviBhaviTrivediFiner, SarahSarahFinerMcQuillin, AndrewAndrewMcQuillinBass, NickNickBassChundru, V KartikV KartikChundruMartin, Hilary CHilary CMartinHuang, Qin QinQin QinHuangValkovskaya, MariaMariaValkovskayaChu, Chia-YiChia-YiChuKanjira, SusanSusanKanjiraPO-HSIU KUOHSI-CHUNG CHENTsai, Shih-JenShih-JenTsaiLiu, Yu-LiYu-LiLiuKendler, Kenneth SKenneth SKendlerPeterson, Roseann ERoseann EPetersonCai, NaNaCaiFang, YuYuFangSen, SrijanSrijanSenScott, Laura JLaura JScottBurmeister, MargitMargitBurmeisterLoos, Ruth J FRuth J FLoosPreuss, Michael HMichael HPreussActkins, Ky'Era VKy'Era VActkinsDavis, Lea KLea KDavisUddin, MonicaMonicaUddinWani, Agaz HAgaz HWaniWildman, Derek EDerek EWildmanAiello, Allison EAllison EAielloUrsano, Robert JRobert JUrsanoKessler, Ronald CRonald CKesslerKanai, MasahiroMasahiroKanaiOkada, YukinoriYukinoriOkadaSakaue, SaoriSaoriSakaueRabinowitz, Jill AJill ARabinowitzMaher, Brion SBrion SMaherUhl, GeorgeGeorgeUhlEaton, WilliamWilliamEatonCruz-Fuentes, Carlos SCarlos SCruz-FuentesMartinez-Levy, Gabriela AGabriela AMartinez-LevyCampos, Adrian IAdrian ICamposMillwood, Iona YIona YMillwoodChen, ZhengmingZhengmingChenLi, LimingLimingLiWassertheil-Smoller, SylviaSylviaWassertheil-SmollerJiang, YunxuanYunxuanJiangTian, ChaoChaoTianMartin, Nicholas GNicholas GMartinMitchell, Brittany LBrittany LMitchellByrne, Enda MEnda MByrneAwasthi, SwapnilSwapnilAwasthiColeman, Jonathan R IJonathan R IColemanRipke, StephanStephanRipkeSofer, TamarTamarSoferWalters, Robin GRobin GWaltersMcIntosh, Andrew MAndrew MMcIntoshPolimanti, RenatoRenatoPolimantiDunn, Erin CErin CDunnStein, Murray BMurray BSteinGelernter, JoelJoelGelernterLewis, Cathryn MCathryn MLewisKuchenbaecker, KarolineKarolineKuchenbaecker2024-01-292024-01-292024-01-0410614036https://scholars.lib.ntu.edu.tw/handle/123456789/639135Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.en[SDGs]SDG3Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inferencejournal article10.1038/s41588-023-01596-4381773452-s2.0-85181441322https://api.elsevier.com/content/abstract/scopus_id/85181441322