Association of Polygenic Risk Scores for Neurodevelopmental Traits and Psychiatric Conditions with Incontinence and Constipation in Children and Young People

Observational studies report prospective associations of neurodevelopmental and psychiatric traits with paediatric incontinence and constipation, but unmeasured and residual confounding may limit observational measures. Here, we use a prospective birth cohort study to investigate whether common variant genetic liability for a range of neurodevelopmental and psychiatric conditions are associated with paediatric incontinence and constipation. We used data from 7,857 participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) with data on genotype, incontinence, and constipation, and calculated Polygenic risk scores (PRS) for neurodevelopmental traits (ADHD, autism, intelligence) and psychiatric conditions (anxiety, depression, and OCD). Incontinence subtypes (daytime urinary incontinence [DUI], enuresis [any bedwetting and enuresis subtypes: monosymptomatic, non-monosymptomatic], faecal incontinence), and constipation, were assessed by parental reports at age 9 years and self-reports at age 14. PRS for ADHD (OR=1.14, 95% CI, 1.01-1.29, unadjusted p=0.040) and depression (OR=1.09, 95% CI, 1.00-1.20, unadjusted p=0.063) were associated with DUI at age 9. PRS for autism (OR=1.19, 95% CI, 1.02-1.41, unadjusted p=0.032) and intelligence (OR=1.17, 95%, 0.99-1.38, unadjusted p=.06l) were associated with DUI at age 14. PRS for ADHD (OR=1.13, 95% CI, 1.03-1.24, unadjusted p=0.008) were associated with constipation at age 9. Within enuresis subtypes, PRS for autism were associated with MNE at age 9 (OR=1.15, 95% CI, 1.03-1.28, unadjusted p=0.012), but not NMNE (OR=0.93, 95% CI, 0.79-1.18, unadjusted p=0.335). No associations survived false discovery rate adjustment. The findings add to existing evidence that common variant genetic liability for neurodevelopmental traits and psychiatric conditions could be associated with paediatric incontinence and constipation. Key pointsO_ST_ABSQuestionC_ST_ABSAre common variant genetic liabilities for neurodevelopmental and psychiatric conditions associated with paediatric incontinence and constipation in a population-based cohort? FindingsWe found some evidence that polygenic risk scores (PRS) for ADHD, autism, intelligence, and depression may be associated with daytime urinary incontinence. PRS for ADHD were also associated with constipation and enuresis and PRS for autism and depression were weakly associated with constipation. None of the associations survived adjustment for false discovery rate. MeaningCommon variant genetic liabilities for ADHD, autism, intelligence, and depression could be risk factors for developing paediatric incontinence and constipation.