DESCRIPTION:
GWAS summary statistics were selected from publicly-available GWAS of individuals of European ancestry on a variety of internalizing, externalizing, and substance use traits. Selection of externalizing psychopathology and substance use traits was partly based on a recent genomic SEM investigation of externalizing and included three measures of substance use: lifetime cannabis use (N=162,082), lifetime smoking initiation (N=632,802), and the number of alcoholic drinks per week (N=537,349). Additionally, we included four measures of non-substance use externalizing problems, including attention-deficit/hyperactivity disorder (ADHD; N=55,290), general risk tolerance and speeding behavior (N=939,908), reverse-coded age at first sexual intercourse (N=317,694) and number of sexual partners (N=370,711) obtained from the UK Biobank (http://www.nealelab.is/uk-biobank/), and antisocial behavior. Target data were drawn from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative sample of 20,745 youth starting in grades 7-12 in the United States. Specifically, substance use and demographic data were drawn from the Wave IV survey, which occurred from 2008-2009, on a subset of participants (N=15,071). Participants ranged in age from 24-34 (mean age=28.98 years; SD=1.75). The three resulting higher-order factors represented: 1) substance use (SU)-related psychopathology (including variance shared across substance use, internalizing, and externalizing psychopathology), 2) variance in internalizing traits not related to substance use (non-SU internalizing), and 3) variance in externalizing traits not related to substance use (non-SU externalizing). We calculated the effective n’s for each factor consistent with the approach in Demange, Malanchini (23); these sample sizes are as follows: 1,734,340 (SU psychopathology-related), 1,164,731 (Non-SU internalizing), and 730,198 (Non-SU externalizing). After performing Q-SNP analysis, 1,720 Q-SNPs were removed, leaving 1,557,030 SNPs for analysis. No gene sets passed Bonferroni correction in the MAGMA gene-set analysis. MAGMA gene-property tissue expression analyses implicated the pituitary and several brain tissues (cortex, cerebellum, and nucleus accumbens), as well as early-prenatal and early-mid-prenatal developmental stages of brain tissue.
LABEL:
MAGMA genes associated with SU factor_pvalue
SCORE TYPE:
P-Value
THRESHOLD:
<= 0.5
GENES IN THRESHOLD:
8967
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ABSTRACT:
Genes in threshold: 8967
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