A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.
Tin AungMineo OzakiTakanori MizoguchiR Rand AllinghamZheng LiAravind HaripriyaSatoko NakanoSteffen UebeJeffrey M HarderAnita S Y ChanMei Chin LeeKathryn P BurdonYury S AstakhovKhaled K Abu-AmeroJuan C ZentenoYildirim NilgünTomasz ZarnowskiMohammad PakravanLeen Abu SafiehLiyun JiaYa Xing WangSusan Eileen Isabella WilliamsDaniela PaoliPatricio G SchlottmannLulin HuangKar-Seng SimJia-Nee FooMasakazu NakanoYoko IkedaRajesh S KumarMorio UenoShin-ichi ManabeKen HayashiShigeyasu KazamaRyuichi IdetaYosai MoriKazunori MiyataKazuhisa SugiyamaTomomi HigashideEtsuo ChiharaKenji InoueSatoshi IshikoAkitoshi YoshidaMasahide YanagiYoshiaki KiuchiMakoto AiharaTsutomu OhashiToshiya SakuraiTakako SugimotoHideki ChumanFumihiko MatsudaKenji YamashiroNorimoto GotohMasahiro MiyakeSergei Y AstakhovEssam A OsmanSaleh A Al-ObeidanOhoud OwaidhahLeyla Al-JasimSami Al ShahwanRhys A FogartyPaul LeoYaz YetkinÇilingir OğuzMozhgan Rezaei KanaviAfsaneh Nederi BeniShahin YazdaniEvgeny L AkopovKai-Yee TohGareth R HowellAndrew C OrrYufen GohWee Yang MeahSu Qin PehEwa Kosior-JareckaUrszula LukasikMandy KrumbiegelEranga N VithanaTien Yin WongYutao LiuAllison E Ashley KochPratap ChallaRobyn M RautenbachDavid A MackeyAlex W HewittPaul MitchellJie Jin WangAri ZiskindTrevor CarmichaelRangappa RamakrishnanKalpana NarendranRangaraj VenkateshSaravanan VijayanPeiquan ZhaoXueyi ChenDalia Guadarrama-VallejoChing Yu ChengShamira A PereraRahat HusainSu-Ling HoUlrich-Christoph Welge-LuessenChristian MardinUrsula Schloetzer-SchrehardtAxel M HillmerStefan HermsSusanne MoebusMarkus M NöthenNicole WeisschuhRohit ShettyArkasubhra GhoshYik Ying TeoMatthew A BrownIgnacio Lischinskynull nullnull nullJonathan G CrowstonMichael CooteBowen ZhaoJinghong SangNihong ZhangQi Sheng YouVera VysochinskayaPanayiota FountiAnthoula ChatzikyriakidouAlexandros LambropoulosEleftherios AnastasopoulosAnne L ColemanM Roy WilsonDouglas J RheeJae Hee KangInna May-BolchakovaSteffen HeegaardKazuhiko MoriWallace L M AlwardJost Bruno JonasLiang XuJeffrey M LiebmannBalram ChowbayElke SchaeffelerMatthias SchwabFabian LernerNingli WangZhenglin YangPaolo FrezzottiShigeru KinoshitaJohn H FingertMasaru InataniKei TashiroAndré ReisDeepak P EdwardLouis R PasqualeToshiaki KubotaJaney L WiggsFrancesca PasuttoFotis TopouzisMichael DubinaJamie E CraigNagahisa YoshimuraPeriasamy SundaresanSimon W M JohnRobert RitchMichael A HauserChiea-Chuen KhorPublished in: Nature genetics (2015)
Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.