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Chunk #37 — METHODS — Post-hoc analyses of European ancestry GWAS results — Biological Characterization

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Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders.
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FUMA23 was used for post-hoc bioinformatic analyses of our five GWAS (i.e., the addiction-rf (from Genomic SEM), PAU-specific, PTU-specific, CUD-specific, OUD-specific (from ASSET) loci) in European ancestry samples and to determine lead and independent variants. Within FUMA, gene-based tests and gene-set enrichment were conducted via MAGMA57; gene annotation, and identification of SNP-to-gene associations via expression quantitative trait loci (eQTLs) and/or chromatin interactions (via Hi-C data) in PsychEncode58 and Roadmap Epigenomics tissues for Prefrontal cortex, hippocampus, ventricles, and neural progenitor cells59,60. For each specific SUD GWAS run using ASSET, the distribution of p-values included all non-pleiotropic SNPs (i.e., SNPs only associated with a single SUD, n SNP CUD-Specific = 312,661, n SNP PTU-Specific = 560,983, n SNP PAU-Specific = 193,647, n SNP OUD-Specific = 425,665). Additional details on the FUMA analyses are available in Online Methods.