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

Abstract

The 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.

Benchmarking post-GWAS analysis tools in major depression: Challenges and implications

“…PCOLCE2 is highly expressed in the pituitary and there is evidence of reduced levels in depression-like behaviours in mice ( Yamawaki et al, 2018 ), consistent with rs9757063 effect. Indeed, it has already been associated with psychiatric disorders by GWAS studies ( Martínez-Magaña et al, 2021 ). However, how exactly they play a role in MD pathogenesis is still unknown.…”

The Prevalence of Symptomatology and Risk Factors in Mental Health in Mexico: The 2016–17 ENCODAT Cohort

“…This scale has shown a high level of consensus among interviewers (kappa = 0.8), with the best consensus for estimations of the presence of disorders during the lifetime of the interviewee [ 8 ]. It includes the evaluation of symptomatology of psychosis, depression, anxiety, obsession/compulsion, mania/hypomania, and post-traumatic stress [ 9 ]. The analysis also employed data taken from the first stage of the survey related to suicide attempts and pathological gambling [ 10 , 11 ].…”

“…A positive response was defined as having been diagnosed with schizophrenia or meeting the following two criteria: (1) having experienced a period of hearing voices when no one was present or having visions or seeing things that others could not see, and (2) having had ideas or beliefs that others did not share or that turned out not to be true [ 8 , 9 ].…”

“…A positive response was defined as having had the following three symptoms: (1) having experienced a sudden feeling of anxiety or fear; (2) having, as part of that experience, an accelerated heart rate, chest pains, shortness of breath, a choking sensation, nausea, sweating, weakness, or the fear of going crazy or dying; and (3) having these feelings worsen or intensify in the first ten minutes [ 8 , 9 ].…”

“…A positive response was defined as “having ever felt depressed, sad, or discouraged almost every day for two weeks or more” and also meeting one of the following criteria: (1) having ever lost most or all interest in normal activities for two weeks or more, (2) having had feelings of uselessness or guilt during that period, or spent a lot of time with thoughts of death, suicide, or self-harm, or (3) having noted significant changes in appetite during that period, or unexpected gain or loss in weight, changes in normal sleep patterns, or difficulty concentrating [ 8 , 9 ].…”