Iglesias, Adriana IAdriana IIglesiasMishra, AniketAniketMishraVitart, VeroniqueVeroniqueVitartBykhovskaya, YelenaYelenaBykhovskayaHöhn, René Gerhard JoachimRené Gerhard JoachimHöhn0000-0003-2870-1469Springelkamp, HenriëtHenriëtSpringelkampCuellar-Partida, GabrielGabrielCuellar-PartidaGharahkhani, PuyaPuyaGharahkhaniBailey, Jessica N CookeJessica N CookeBaileyWilloughby, Colin EColin EWilloughbyLi, XiaohuiXiaohuiLiYazar, SeyhanSeyhanYazarNag, AbhishekAbhishekNagKhawaja, Anthony PAnthony PKhawajaPolašek, OzrenOzrenPolašekSiscovick, DavidDavidSiscovickMitchell, PaulPaulMitchellTham, Yih ChungYih ChungThamHaines, Jonathan LJonathan LHainesKearns, Lisa SLisa SKearnsHayward, CarolineCarolineHaywardShi, YuanYuanShivan Leeuwen, Elisabeth MElisabeth Mvan LeeuwenTaylor, Kent DKent DTaylorBonnemaijer, PieterPieterBonnemaijerRotter, Jerome IJerome IRotterMartin, Nicholas GNicholas GMartinZeller, TanjaTanjaZellerMills, Richard ARichard AMillsStaffieri, Sandra ESandra EStaffieriJonas, Jost BJost BJonasSchmidtmann, IreneIreneSchmidtmannBoutin, ThibaudThibaudBoutinKang, Jae HJae HKangLucas, Sionne E MSionne E MLucasWong, Tien YinTien YinWongBeutel, Manfred EManfred EBeutelWilson, James FJames FWilsonUitterlinden, André GAndré GUitterlindenVithana, Eranga NEranga NVithanaFoster, Paul JPaul JFosterHysi, Pirro GPirro GHysiHewitt, Alex WAlex WHewittKhor, Chiea ChuenChiea ChuenKhorPasquale, Louis RLouis RPasqualeMontgomery, Grant WGrant WMontgomeryKlaver, Caroline C WCaroline C WKlaverAung, TinTinAungPfeiffer, NorbertNorbertPfeifferMackey, David ADavid AMackeyHammond, Christopher JChristopher JHammondCheng, Ching-YuChing-YuChengCraig, Jamie EJamie ECraigRabinowitz, Yaron SYaron SRabinowitzWiggs, Janey LJaney LWiggsBurdon, Kathryn PKathryn PBurdonvan Duijn, Cornelia MCornelia Mvan DuijnMacGregor, StuartStuartMacGregor2024-10-252024-10-252018-05-14https://boris-portal.unibe.ch/handle/20.500.12422/162207Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.en600 - Technology::610 - Medicine & healtharticle10.7892/boris.1168382976044210.1038/s41467-018-03646-6