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Chunk #43 — Methods — eQTL integrative analysis.

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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.
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A transcriptome-wide association study (TWAS) was conducted using the precomputed gene expression weights from PsychENCODE data (1,321 brain samples)43, available online with the FUSION software42. For genes with significant cis-SNP heritability (13,435 genes), FUSION software (vOct 1, 2019) was used to test whether SNPs influencing gene expression are also associated with BD (Bonferroni-corrected P-value threshold < 3.72 × 10−6). For regions including a TWAS significant gene, TWAS fine-mapping of the region was conducted using FOCUS (fine-mapping of causal gene sets, v0.6.10)44. Regions were defined using the correlation matrix of predicted effects on gene expression around TWAS significant genes44. A posterior inclusion probability (PIP) was assigned to each gene for being causal for the observed TWAS association signal. Based on the PIP of each gene and a null model, whereby no gene in the region is causal for the TWAS signal, the 90%-credible gene set for each region was computed44.