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Chunk #33 — Results — Pathway and functional genomic analyses

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Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank.
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Using the GTEx database (http://www.broadinstitute.org/gtex/), 25 multi-tissue cis-eQTL associations were identified for 16 independent lead SNPs with meta-analysis P < 1 × 10−5 (Supplementary Tables 4, 6, 8, 10, and 14). The 5 genome-wide significant SNPs identified for mMDD show eQTL evidence for the genes GLB1 and CRTAP. Random effect meta-analysis of multi-tissues for the most significant mMDD SNP, rs447803, yielded P = 3.58 × 10−9 and 8.45 × 10−29 for GLB1 and CRTAP, respectively. For this study, data mining of regulatory elements was restricted to normal cell lines/tissues. There was evidence of regulatory elements (Regulome DB score < 4) for 6 of the lead SNPs with meta-analysis P ≤ 1 × 10−5 (MDD: rs10736455, rs73249855, rs8050755; rMDD: rs60716536; fMDD: rs11613048; mMDD: rs74002781). Of the six SNPs which achieved genome-wide significance in the meta-analysis of mMDD, 2 SNPs (rs11558338 and rs6809511) showed evidence of transcription factor binding, position weight matrix, histone modification, DNase hypersensitivity, and FAIRE regulatory elements. Evidence of regulatory evidence for all independent SNPs with meta-analysis P ≤ 1 × 10−5 are shown in Supplementary Table 14.