Exploring the Genetic Risk of Childhood Daytime Urinary Incontinence: A Genome-Wide Association Study.
| Autor: | Breinbjerg A; Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Jørgensen CS; Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Walters GB; deCODE genetics/Amgen, Reykjavík, Iceland.; Faculty of Medicine, University of Iceland, Reykjavík, Iceland., Grove J; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen and Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.; Centre for Genomics and Personalized Medicine, CGPM, Aarhus University, Aarhus, Denmark.; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark., Als TD; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen and Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.; Centre for Genomics and Personalized Medicine, CGPM, Aarhus University, Aarhus, Denmark., Kamperis K; Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Stéfansdóttir L; deCODE genetics/Amgen, Reykjavík, Iceland., Thirstrup JP; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen and Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Centre for Genomics and Personalized Medicine, CGPM, Aarhus University, Aarhus, Denmark., Borg B; Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Albiñana C; NCRR - National Centre for Register-based Research, Aarhus University, Aarhus, Denmark., Vilhjálmsson BJ; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen and Aarhus, Denmark.; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.; NCRR - National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.; Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Eðvarðsson VÖ; Faculty of Medicine, University of Iceland, Reykjavík, Iceland.; Children's Medical Center, Landspitali-The National University Hospital of Iceland, Reykjavík, Iceland., Stefánsson H; deCODE genetics/Amgen, Reykjavík, Iceland., Mortensen PB; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen and Aarhus, Denmark.; NCRR - National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.; CIRRAU-Center for Integrated Register-based Research, Aarhus University, Aarhus, Denmark., Agerbo E; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen and Aarhus, Denmark.; NCRR - National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.; CIRRAU-Center for Integrated Register-based Research, Aarhus University, Aarhus, Denmark., Werge T; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen and Aarhus, Denmark.; Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Børglum A; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen and Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.; Centre for Genomics and Personalized Medicine, CGPM, Aarhus University, Aarhus, Denmark., Demontis D; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen and Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Centre for Genomics and Personalized Medicine, CGPM, Aarhus University, Aarhus, Denmark.; Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Stefánsson K; deCODE genetics/Amgen, Reykjavík, Iceland.; Faculty of Medicine, University of Iceland, Reykjavík, Iceland., Rittig S; Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Christensen JH; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen and Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.; Centre for Genomics and Personalized Medicine, CGPM, Aarhus University, Aarhus, Denmark. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of urology [J Urol] 2024 Dec; Vol. 212 (6), pp. 851-861. Date of Electronic Publication: 2024 Aug 02. |
| DOI: | 10.1097/JU.0000000000004187 |
| Abstrakt: | Purpose: Childhood incontinence is stigmatized and underprioritized, and a basic understanding of its pathogenesis is missing. Our goal was to identify risk-conferring genetic variants in daytime urinary incontinence (DUI). Materials and Methods: We conducted a genome-wide association study in the Danish iPSYCH2015 cohort. Cases (3024) were identified through DUI diagnosis codes and redeemed prescriptions for DUI medication in individuals aged 5 to 20 years. Controls (30,240), selected from the same sample, were matched to cases on sex and psychiatric diagnoses, if any, and down-sampled to a 1:10 case:control ratio. Replication was performed in the Icelandic deCODE cohort (5475 cases/287,773 controls). Single-nucleotide polymorphism heritability was calculated using the genome-based restricted maximum likelihood method. Cross-trait genetic correlation was estimated using linkage disequilibrium score regression. Polygenic risk scores generated with LDpred2-auto and BOLT-LMM were assessed for association. Results: Variants on chromosome 6 (rs12210989, odds ratio [OR] 1.24, 95% CI 1.17-1.32, P = 3.21 × 10 -12 ) and 20 (rs4809801, OR 1.18, 95% CI 1.11-1.25, P = 3.66 × 10 -8 ) reached genome-wide significance and implicated the PRDM13 and RIPOR3 genes. Chromosome 6 findings were replicated ( P = .024, OR 1.09, 95% CI 1.01-1.16). Liability scale heritability ranged from 10.20% (95% CI 6.40%-14.00%) to 15.30% (95% CI 9.66%-20.94%). DUI and nocturnal enuresis showed positive genetic correlation ( r Conclusions: Common genetic variants contribute to the risk of childhood DUI, and genes important in neuronal development and detrusor smooth muscle activity were implicated. These findings may help guide identification of new treatment targets. |
| Databáze: | MEDLINE |
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