Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals

AbstractThe combination of substance use and psychiatric disorders is one of the most common comorbidities. The objective of this study was to perform a genome-wide association study of this comorbidity (Com), substance use alone (Subs), and psychiatric symptomatology alone (Psych) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (p < 5.00e−05). The SNPs associated with each trait were independent, and the individuals with high PRSs had a higher prevalence of tobacco and alcohol use. In the multinomial models all of the PRSs (Subs-PRS, Com-PRS, and Psych-PRS) were associated with all of the traits. Brain meQTL of the Subs-associated SNPs had an effect on the genes enriched in insulin signaling pathway, and that of the Psych-associated SNPs had an effect on the Fc gamma receptor phagocytosis pathway.

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Genome-Wide Association Study of Opioid Cessation

Journal of Clinical Medicine ◽

10.3390/jcm9010180 ◽

2020 ◽

Vol 9 (1) ◽

pp. 180 ◽

Cited By ~ 1

Author(s):

Jiayi W. Cox ◽

Richard M. Sherva ◽

Kathryn L. Lunetta ◽

Emma C. Johnson ◽

Nicholas G. Martin ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Chronic Back Pain ◽

The United States ◽

Genome Wide Association ◽

European Ancestry ◽

Risk Scores ◽

Opioid Use ◽

Genome Wide ◽

A Genome

The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in PTPRD (pAA + EA = 2.24 × 10−6), rs36098404 in MYOM2 (pEA = 2.24 × 10−6), and rs592026 in SNAP25-AS1 (pEA = 6.53 × 10−6). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10−2) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10−2). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD.

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