Estimating the Direct Effects of the Genetic Liabilities to Bipolar Disorder, Schizophrenia, and Behavioral Traits on Suicide Attempt Using a Multivariable Mendelian Randomization Approach

Authors

Brenda Cabrera-Mendoza
Necla Aydin
Gabriel R Fries
Anna R Docherty
Consuelo Walss-Bass
Renato Polimanti

Publication Date

8-1-2024

Journal

Neuropsychopharmacology

DOI

10.1038/s41386-024-01833-2

PMID

38396255

PMCID

PMC11250798

PubMedCentral® Posted Date

2-23-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Bipolar disorder (BD) and schizophrenia (SZ) are associated with higher odds of suicide attempt (SA). In this study, we aimed to explore the effect of BD and SZ genetic liabilities on SA, also considering the contribution of behavioral traits, socioeconomic factors, and substance use disorders. Leveraging large-scale genome-wide association data from the Psychiatric Genomics Consortium (PGC) and the UK Biobank (UKB), we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the putative causal effect of BD (41,917 cases, 371,549 controls) and SZ (53,386 cases, 77,258 controls) on SA (26,590 cases, 492,022 controls). Then, we assessed the putative causal effect of BD and SZ on behavioral traits, socioeconomic factors, and substance use disorders. Considering the associations identified, we evaluated the direct causal effect of behavioral traits, socioeconomic factors, and substance use disorders on SA using a multivariable MR approach. The genetic liabilities to BD and SZ were associated with higher odds of SA (BD odds ratio (OR) = 1.24, p = 3.88 × 10-12; SZ OR = 1.09, p = 2.44 × 10-20). However, while the effect of mental distress (OR = 1.17, p = 1.02 × 10-4) and risk-taking (OR = 1.52, p = 0.028) on SA was independent of SZ genetic liability, the BD-SA relationship appeared to account for the effect of these risk factors. Similarly, the association with loneliness on SA was null after accounting for the effect of SZ genetic liability. These findings highlight the complex interplay between genetic risk of psychiatric disorders and behavioral traits in the context of SA, suggesting the need for a comprehensive mental health assessment for high-risk individuals.

Keywords

Humans, Mendelian Randomization Analysis, Schizophrenia, Bipolar Disorder, Suicide, Attempted, Genome-Wide Association Study, Genetic Predisposition to Disease, Substance-Related Disorders, Socioeconomic Factors, Male, Polymorphism, Single Nucleotide, Female

Published Open-Access

yes

Recommended Citation

Cabrera-Mendoza, Brenda; Aydin, Necla; Fries, Gabriel R; et al., "Estimating the Direct Effects of the Genetic Liabilities to Bipolar Disorder, Schizophrenia, and Behavioral Traits on Suicide Attempt Using a Multivariable Mendelian Randomization Approach" (2024). Faculty, Staff and Student Publications. 4380.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4380