Background Observational studies have found that depression and anxiety are prospectively associated with lower urinary tract symptoms (LUTS), but these studies are limited by potential environmental confounding and measurement error. Using genetic liability for psychiatric traits offers an alternative approach.

Objectives Examine the association of genetic liability for depression, anxiety, and neuroticism with LUTS in women.

Methods Data: i) Avon Longitudinal Study of Parents and Children (ALSPAC) Mothers Cohort. ii) GWAS (genome-wide association study) summary data on psychiatric traits.

Exposures: Polygenic risk scores (PRS) for depression, anxiety, and neuroticism.

Outcomes: LUTS - assessed in 2002-04 (mean [sd] age = 40.3 [4.6]) and 2011-12 (49.7 [4.5]) using validated questionnaires.

Statistical analysis: Logistic regression adjusted for age and population structure.

Key findings and limitations The neuroticism PRS was associated with nocturia at both time points [odds ratio and 95% confidence intervals=1.24 (1.10,1.40) and 1.21 (1.07,1.37)], and with any UI, any urgency, and mixed UI (2002-04 only) [1.14 (1.05,1.23), 1.12 (1.02,1.23), and 1.23 (1.07,1.43), respectively]. The depression PRS was associated with nocturia [1.33 (1.17,1.50) and 1.24 (1.09,1.40)] and any UI [1.09 (1.01,1.18); 1.11 (1.02,1.20)] at both timepoints, and with any urgency (2011-12 only) [1.13 (1.03,1.24)]. The anxiety PRS was associated with mixed UI (2002-04 only) [1.20 (1.03,1.39)].

PRS may not capture all genetic liability and cannot account for pleiotropic effects. The ALSPAC cohort includes only parous women and is predominantly affluent and of European ancestry.

Conclusions and clinical implications Genetic liability for depression, anxiety and neuroticism was associated with LUTS in women, suggesting psychiatric factors may contribute to the aetiology of LUTS.

Patient summary In this study we looked at whether parous women with a high genetic risk of mental health problems were more likely to have urinary symptoms. We found various associations, with the strongest evidence found for genetic liability to depression and neuroticism increasing the risk of nocturia (waking during the night to pass urine). Our findings suggest that psychiatric factors could be important in understanding urinary symptoms, and more research is needed to find out if this these associations apply to other demographics.

The authors have declared no competing interest.

The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. Genomewide genotyping data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. This research was funded in whole, or in part, by the Wellcome Trust [Grant number: 218495/Z/19/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work is supported by funding from the Medical Research Council (grant ref: MR/V033581/1: Mental Health and Incontinence). This publication is the work of the authors and they will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). The funder had no role in the study design; collection, analysis and interpretation of data; writing of the report; and the decision to submit the article for publication.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. Consent for biological samples has been collected in accordance with the Human Tissue Act (2004). Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time. Specific details on the ethics committees and institutional review boards are available here: http://www.bristol.ac.uk/alspac/researchers/research-ethics/

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Access to ALSPAC research data must be requested using the formal procedures (outlined at: https://www.bristol.ac.uk/alspac/researchers/access/) and is subject to eligibility, compliance against the ALSPAC funders terms and conditions and University of Bristol policies and procedures.