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. 2024 Dec;212(6):851-861.
doi: 10.1097/JU.0000000000004187. Epub 2024 Aug 2.

Exploring the Genetic Risk of Childhood Daytime Urinary Incontinence: A Genome-Wide Association Study

Anders Breinbjerg  1   2 , Cecilie Siggaard Jørgensen  1   2 , G Bragi Walters  3   4 , Jakob Grove  5   6   7   8   9 , Thomas D Als  5   6   7   8 , Konstantinos Kamperis  1   2 , Lilja Stéfansdóttir  3 , Janne P Thirstrup  5   6   8 , Britt Borg  1   2 , Clara Albiñana  10 , Bjarni J Vilhjálmsson  5   9   10   11 , Viðar Ö Eðvarðsson  4   12 , Hreinn Stefánsson  3 , Preben B Mortensen  5   10   13 , Esben Agerbo  5   10   13 , Thomas Werge  5   14   15 , Anders Børglum  5   6   7   8 , Ditte Demontis  5   6   8   11 , Kári Stefánsson  3   4 , Søren Rittig  1   2 , Jane Hvarregaard Christensen  5   6   7   8
Affiliations

Exploring the Genetic Risk of Childhood Daytime Urinary Incontinence: A Genome-Wide Association Study

Anders Breinbjerg et al. J Urol. 2024 Dec.

Abstract

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 (rg = 1.28 ± 0.38, P = .0007). DUI was associated with attention-deficit/hyperactivity disorder (OR 1.098, 95% CI 1.046-1.152, P < .0001) and BMI (OR 1.129, 95% CI 1.081-1.178, P < .0001) polygenic risk.

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.

Keywords: child; diurnal enuresis; genetic loci; genome-wide association study; urinary incontinence.

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Comment in

  • Editorial Comment.
    Jhaveri H, Gbadegesin R. Jhaveri H, et al. J Urol. 2024 Dec;212(6):861. doi: 10.1097/JU.0000000000004201. Epub 2024 Aug 22. J Urol. 2024. PMID: 39172810 No abstract available.

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