Cross-phenotype relationship between opioid use disorder and suicide attempts: new evidence from polygenic association and Mendelian randomization analyses
Recommended Citation
Huang Y, Chen D, Levin AM, Ahmedani BK, Frank C, Li M, Wang Q, Gui H, and Sham PC. Cross-phenotype relationship between opioid use disorder and suicide attempts: new evidence from polygenic association and Mendelian randomization analyses. Mol Psychiatry 2023.
Document Type
Article
Publication Date
6-20-2023
Publication Title
Molecular psychiatry
Abstract
Clinical epidemiological studies have found high co-occurrence between suicide attempts (SA) and opioid use disorder (OUD). However, the patterns of correlation and causation between them are still not clear due to psychiatric confounding. To investigate their cross-phenotype relationship, we utilized raw phenotypes and genotypes from >150,000 UK Biobank samples, and genome-wide association summary statistics from >600,000 individuals with European ancestry. Pairwise association and a potential bidirectional relationship between OUD and SA were evaluated with and without controlling for major psychiatric disease status (e.g., schizophrenia, major depressive disorder, and alcohol use disorder). Multiple statistical and genetics tools were used to perform epidemiological association, genetic correlation, polygenic risk score prediction, and Mendelian randomizations (MR) analyses. Strong associations between OUD and SA were observed at both the phenotypic level (overall samples [OR = 2.94, P = 1.59 ×10(-14)]; non-psychiatric subgroup [OR = 2.15, P = 1.07 ×10(-3)]) and the genetic level (genetic correlation rg = 0.38 and 0.5 with or without conditioning on psychiatric traits, respectively). Consistently, increasing polygenic susceptibility to SA is associated with increasing risk of OUD (OR = 1.08, false discovery rate [FDR] =1.71 ×10(-3)), and similarly, increasing polygenic susceptibility to OUD is associated with increasing risk of SA (OR = 1.09, FDR = 1.73 ×10(-6)). However, these polygenic associations were much attenuated after controlling for comorbid psychiatric diseases. A combination of MR analyses suggested a possible causal association from genetic liability for SA to OUD risk (2-sample univariable MR: OR = 1.14, P = 0.001; multivariable MR: OR = 1.08, P = 0.001). This study provided new genetic evidence to explain the observed OUD-SA comorbidity. Future prevention strategies for each phenotype needs to take into consideration of screening for the other one.
PubMed ID
37340172
ePublication
ePub ahead of print
