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Chunk #46 — Methods — Functional gene mapping — Transcriptome-wide association study (TWAS)

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Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder.
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We performed colocalization analyses using the COLOC R function27,28 implemented in TWAS FUSION. Colocalization is a Bayesian method used to calculate the posterior probabilities (PP) that individual lead SNPs within a significant TWAS locus are (i) independent (e.g., two causal SNPs in LD, one affecting transcription, and one affecting OCD; posterior probability (PP3)) or (ii) share the same associated variant (e.g., a single causal SNP affects both transcription and OCD (PP4)). We also performed a conditional analysis to determine whether identified associations represented independent associations. This was performed using the FUSION software, which jointly estimates the effect of all significant features within each locus by using residual SNP associations with OCD after accounting for the predicted expression of other features.