Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.
Puya GharahkhaniEric JorgensenPirro G HysiAnthony P KhawajaSarah PendergrassXikun HanJue-Sheng OngAlex W HewittAyellet V SegrèJohn M RouhanaAndrew R HamelRobert P IgoHelene ChoquetAyub QassimNavya Shilpa JosyulaJessica N Cooke BaileyPieter W M BonnemaijerAdriana I IglesiasOwen M SiggsTerri L YoungVeronique VitartAlberta A H J ThiadensJuha KarjalainenSteffen UebeRonald B MellesK Saidas NairRobert N LubenMark J SimcoeNishani AmersingheAngela Jane CreeRene HohnAlicia PoplawskiLi Jia ChenShi Song RongTin AungEranga Nishanthie Vithananull nullnull nullnull nullnull nullnull nullnull nullnull nullGen TamiyaYukihiro ShigaMasayuki YamamotoToru NakazawaHannah CurrantEwan BirneyXin WangAdam AutonMichelle K LuptonNicholas G MartinAdeyinka AshayeOlusola Oluyinka OlawoyeSusan Eileen Isabella WilliamsStephen AkafoMichelle RamsayKazuki HashimotoYoichiro KamataniMasato AkiyamaYukihide MomozawaPaul J FosterPeng Tee KhawJames E MorganNicholas G StrouthidisPeter KraftJae Hee KangChi Pui PangFrancesca PasuttoPaul MitchellAndrew John LoteryAarno PalotieCornelia van DuijnJonathan L HainesChristopher J HammondLouis R PasqualeCaroline C W KlaverMichael HauserChiea Chuen KhorDavid A MackeyMichiaki KuboChing-Yu ChengJamie E CraigStuart MacgregorJaney L WiggsPublished in: Nature communications (2021)
Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.