PD48-01 UNCOVERING GENETIC PREDISPOSITION OF PEYRONIE’S DISEASE (PD) THROUGH DUPUYTREN’S DISEASE (DD): A GENOME WIDE ASSOCIATION STUDY (GWAS) OF THE UK BIOBANK

You have accessJournal of UrologySexual Function/Dysfunction: Peyronie's Disease (PD48)1 Sep 2021PD48-01 UNCOVERING GENETIC PREDISPOSITION OF PEYRONIE’S DISEASE (PD) THROUGH DUPUYTREN’S DISEASE (DD): A GENOME WIDE ASSOCIATION STUDY (GWAS) OF THE UK BIOBANK Matthew Sloan, Jun Wei, Rong Na, Joshua Halpern, Zhuqing Shi, Jianfeng Xu, Brian Helfand, and Richard Fantus Matthew SloanMatthew Sloan More articles by this author , Jun WeiJun Wei More articles by this author , Rong NaRong Na More articles by this author , Joshua HalpernJoshua Halpern More articles by this author , Zhuqing ShiZhuqing Shi More articles by this author , Jianfeng XuJianfeng Xu More articles by this author , Brian HelfandBrian Helfand More articles by this author , and Richard FantusRichard Fantus More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002070.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While PD is a relatively rare condition, it is often associated with other more prevalent fibroconnective disorders including DD. PD likely represents a heterogeneous condition, with both heritable and environmentally-driven factors contributing to its development and progression. Despite advances in genotyping techniques, there remains a significant gap in understanding PD’s cause and heritability. Therefore, we sought to further define the heritable component of PD by performing a GWAS on men with DD and subsequently validating the findings in an independent cohort of men with PD. METHODS: Using the United Kingdom Biobank (UKB), a prospective database containing 500,000 participants with both genetic data and health care information (with an average of 9.3 years of follow-up), we first confirmed the association between PD and DD. We then conducted a multi-stage GWAS of Caucasian men with DD with subsequent validation cohort consisting of men with PD. RESULTS: Among 215,065 men, 3,539 (1.65%) carried a diagnosis of DD and 1,012 (0.47%) carried a diagnosis with PD. Men with PD had a significantly higher risk of DD (OR 2.78, CI 2.04-3.69); p=1.48x10-11), and inversely men with PD had a significantly higher risk of DD (OR 2.82, CI 2.07-3.75); p=7.05x10-12). Despite these odds, there were still a significant number of men with only PD or DD and not both disorders (Figure). The GWAS of DD identified 54 significant loci (p <5x10-8), including 32 novel loci. Analysis of these loci in men with PD revealed significant associations at rs10453460 (C) within WNT7B (OR=1.20; 3.53x10-4) and rs1022648 (A) within WNT2 (OR=1.19; p=1.57x10-4). CONCLUSIONS: Given the low frequency of its clinical presentation, the heritability of PD has been challenging to study. By conducting a GWAS for a related fibroconnective disorder, DD, we have elucidated some potential heritable explanations for PD within the WNT signaling pathways. Not only have we validated previous studies demonstrating a relationship between WNT2 and DD but we have found potentially novel associations between WNT7B and PD. Future large scale studies in more diverse cohorts are needed to validate these findings. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e838-e838 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Sloan More articles by this author Jun Wei More articles by this author Rong Na More articles by this author Joshua Halpern More articles by this author Zhuqing Shi More articles by this author Jianfeng Xu More articles by this author Brian Helfand More articles by this author Richard Fantus More articles by this author Expand All Advertisement Loading ...