Genetic modification effects of physical frailty on the morbidity of mental disorders in the UK Biobank

Abstract

Objectives: Depression and anxiety are two major categories of mental disorders that are highly prevalent in the general population. This study aims to explore the genetic modification effects of physical frailty on the morbidity of mental disorders.Methods: Using data from UK Biobank, we calculate genetic risk scores for depression, anxiety and mental disorders based on 37/44 single-nucleotide polymorphisms (SNPs) of Major Depressive Disorder (MDD) and 9/10 SNPs of anxiety. Frailty status was defined by a modified version of the frailty phenotype based on five individual components. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of depression and anxiety risk among groups with different frailty status.Results: Of 267,755 participants in UK Biobank, 4,905 (2%) were considered frail, 98,907 (37%) pre-frail and 163,943 (61%) not frail. Compared with the non-frail group, the pre-frail group (HR = 1.53; [95% CI:1.47–1.61]), and frail group (HR = 2.75; [95% CI:2.46–3.07]) were significantly associated with increased risk of depression. Per 1-number increment in frailty component counts were significantly associated with increased risk of mental disorders. In each genetic risk score (GRS) strata, people with pre-frailty and frailty suffered higher risks of mental disorders than the non-frail group.Conclusion: Our results indicate that physical frailty plays an important role in the incidence of mental disorders, even after adjustments for covariates, and patients with genetic individual differences are also affected. Therefore, it is crucial that while diagnosing mental disorders, professionals pay closer attention to those patients who present symptoms of frailty.

Keywords:

• Depression
• anxiety
• mental disorders
• frailty
• genetic risk

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics approval

The UK Biobank study was approved by the National Information Governance Board for Health and Social Care in England and Wales, and the Community Health Index Advisory Group in Scotland and the North West Multicenter Research Ethics Committee. All participants gave written informed consent. This study was also approved by the Ethical Committee of Peking University (Beijing, China).

Authors’ contributions

HL and XG designed the study, YM, NC, JC and NH performed the data interpretation, HL and XG supervised the writing of the statistical analysis and writing of the manuscript, TH performed a critical revision of the manuscript and approved the submitted version of the manuscript. HL confirms full access to all the data in this study and had final responsibility for the decision to submit for publication. All authors have read and agreed to the published version of the manuscript.

Data availability statement

Data are available in a public, open access repository. This research has been conducted using the UK Biobank Resource under Application Number 44430. The UK Biobank data are available on application to the UK Biobank (www.ukbiobank.ac.uk/).

Additional information

Funding

This work was supported by National Natural Science Foundation of China (Grant Number: 72274201 and 71804183).