{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Iglesias AI"],"funding":["NEI NIH HHS","British Heart Foundation","NCATS NIH HHS","Medical Research Council","National Institute for Health Research (NIHR)","NIH HHS"],"pagination":["1864"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5951816"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(1)"],"pubmed_abstract":["Central 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 "],"journal":["Nature communications"],"pubmed_title":["Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases."],"pmcid":["PMC5951816"],"funding_grant_id":["HDR-1004","R01 EY023242","MC_UU_00007/10","UL1 TR001881","R01 EY022305","HDR-9004","G19/2","NF-SI-0617-10113","S10 OD018164","MR/L003120/1","RG/13/13/30194","NF-SI-0512-10165","P30 EY014104","MC_PC_U127561128","R01 EY009052"],"pubmed_authors":["Yazar S","Ricketts M","Martin NG","Zhang K","Vukcevic D","Uitterlinden AG","Gaasterland D","Duncanson A","Sawcer SJ","Moroi SE","Plomin R","Wood NW","Shi Y","Pericak-Vance MA","Schuman JS","Mathew CG","Willoughby CE","Gaasterland T","Band G","Bonnemaijer P","Khawaja AP","Hauser MA","Su Z","Widaa S","Brilliant MH","Hayward C","Holliday EG","Trembath RC","Blackwell JM","Potter SC","Vollrath D","Corvin A","Loomis SJ","Wollstein G","Staffieri SE","Viswanathan A","Bailey JNC","Pasquale LR","Zeller T","Pfeiffer N","Realini A","Weinreb RN","Souzeau E","Allingham RR","Whittaker P","Christen WG","Zack DJ","Deloukas P","Sit AJ","Donnelly P","Pirinen M","Bykhovskaya Y","Khor CC","Wang JJ","Liddle J","Taylor KD","Brown MA","Hewitt AW","Mitchell P","Cuellar-Partida G","Nag A","Giannoulatou E","Hunt SE","Gray E","Mishra A","Hohn R","Pearson R","Kang JH","Klaver CCW","Mackey DA","Rochtchina E","Palmer CNA","Rotter JI","Lee RK","Burdon KP","Lucas SEM","Wilson JF","Aung T","Rautanen A","Inouye M","Lichter PR","Hammond N","Richards JE","Singh K","Gharahkhani P","Xie J","Hammond CJ","Bellenguez C","Kearns LS","McCann OT","Rabinowitz YS","Mills RA","Barroso I","Gwilliam R","Springelkamp H","Edkins S","Markus HS","Freeman C","Casas JP","Spencer CCA","Waller M","Bramon E","van Duijn CM","Cheng CY","Li X","Wong TY","Weston P","Vithana EN","Budenz DL","van Leeuwen EM","MacGregor S","Gillman M","Iglesias AI","Attia J","NEIGHBORHOOD Consortium","Kraft P","Polasek O","Blackburn H","Bumpstead SJ","Beutel ME","Haines JL","Ravindrarajah R","Hysi PG","Liu Y","Langford C","Siscovick D","Scott R","Scott WK","Jankowski J","Schmidtmann I","Montgomery GW","Hellenthal G","Dronov S","Tham YC","Vitart V","Baird PN","Sim X","Wellcome Trust Case Control Consortium 2 (WTCCC2)","Friedman DS","Fingert J","Blue Mountains Eye Study—GWAS group","Jonas JB","Wiggs JL","Foster PJ","Boutin T","Craig JE","Strange A","Jayakumar A"],"additional_accession":[]},"is_claimable":false,"name":"Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.","description":"Central 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 ","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 May","modification":"2026-04-13T07:15:50.277Z","creation":"2019-03-26T22:35:29Z"},"accession":"S-EPMC5951816","cross_references":{"pubmed":["29760442"],"doi":["10.1038/s41467-018-03646-6"]}}