DESCRIPTION:

The genomic structural equation modeling (gSEM) analysis includes results on european ancestry (EA) from the Genetics of Opioid Addiction Consortium (GENOA) meta-analysis, Million Veteran Program (MVP), Psychiatric Genetics Consortium Substance Use Disorders Group (PGC-SUD), and the Partners Health cohorts. The MVP results are based on a meta-analysis including MVP parts 1 and 2 (total of 8529 OUD cases and 71,200 opioid-exposed controls), along with Yale-Penn and Study of Addiction: Genetics and Environment (SAGE) cohorts (total of 10,544 OUD cases and 72,163 opioid-exposed controls). The PGC-SUD results include 4,503 opioid dependence cases and 4173 unexposed controls. Unexposed controls are used for the PGC-SUD because the exposed controls results have negative heritability estimates. The partners health cohort includes 1,039 OUD cases and 10,743 exposed controls. Note that the GENOA GWAS, Yale-Penn, and SAGE parts of the MVP, and the PGC-SUD results include overlapping samples. However, accounting for this sample overlap is a feature of the gSEM approach applied in this study. A total of 2,434,903 variants were present in all cohorts and tested for association with the OA latent variable in the gSEM analysis using a total sample size of 403,915 (23,367 cases and 384,619 controls; effective sample size of 88,114). We applied S-PrediXcan using GTEx version 8 eQTL gene models (http://predictdb.org/) with the gSEM GWAS summary statistics as input to estimate genetically driven differential gene expression in human brain tissues associated with opioid addiction (OA). Fourteen gene-tissue combinations surpassed correction for the total number of gene models and brain tissues (156,215 tests) with a false discovery rate (FDR) less than 0.05 (Table 1; all results presented in Supplementary Table 14). Genes and pvalues presented include those with all FDR values.

LABEL:

Predicted DEG from gSEM GWAS in substantia nigra of OA cases vs. controls_pvalue

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

5126

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ABSTRACT: