Familial Risk and Heritability of Lower Urinary Tract Symptoms in Children and Young Adults

Importance

Lower urinary tract symptoms (LUTS) in children and young adults are common and can significantly impact quality of life. While prior studies suggest a genetic component, the extent of familial aggregation and heritability remains unclear.

Objective

To estimate the familial aggregation and heritability of LUTS in a nationwide cohort of children and young adults.

Design, Setting, and Participants

This population-based cohort study used data from Swedish national registers to identify all live-born singleton children in Sweden between January 1, 1995, and December 31, 2005, with follow-up through December 31, 2018. Familial relationships were determined using the Swedish Multi-Generation Register, and LUTS cases were identified using ICD-10 diagnoses and prescription data from the Swedish National Patient Register and Swedish Prescribed Drug Register.

Exposure

Family history of LUTS, defined by sibling and cousin relationships.

Main Outcomes and Measures

Familial aggregation of LUTS was assessed by estimating relative recurrence risks (RRs) with 95% CIs among siblings and cousins of affected individuals. Heritability was estimated using Falconer’s Liability Threshold Model.

Results

Among 982,903 individuals, LUTS cases were identified using ICD-10, narrow ICD-medication, and broad ICD-medication definitions. Familial aggregation was strongest among siblings, with relative risks of 7.41 (95% CI, 5.72–9.60; P < .001) for storage LUTS and 6.53 (95% CI, 2.09–20.38; P = .001) for voiding LUTS using the narrow ICD-medication definition. Cousin recurrence risks were lower, supporting a genetic contribution to LUTS. Sex-specific analyses showed higher familial aggregation in same-sex sibling pairs, particularly for voiding LUTS in female-female pairs (RR, 14.22; 95% CI, 1.97–102.82; P = .009).

Heritability estimates further supported a genetic basis for LUTS. Storage LUTS heritability was 55% (95% CI, 45.5%–64.7%) using the narrow ICD-medication definition and 48% (95% CI, 46.8%–48.6%) using the broad definition. Voiding LUTS heritability was lower, at 40% (95% CI, 37.6%–43.2%) and 26% (95% CI, 14.8%–37.7%) for the narrow and broad definitions, respectively.

Conclusions and Relevance

These findings provide strong evidence for a genetic contribution to LUTS in children and young adults, with higher familial aggregation among closely related individuals and same-sex sibling pairs. The moderate to high heritability estimates suggest that genetic factors play a key role in LUTS susceptibility, with potential sex-specific influences. These findings may inform risk stratification, early intervention strategies, and future genetic research.

Key Points