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Chunk #54 — ONLINE METHODS — Gene-wise and pathway analysis

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Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.
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Our approach was guided by rigorous method comparisons conducted by PGC members55,99. P-values quantifying the degree of association of genes and gene sets with MDD were generated using MAGMA (v1.06)100. MAGMA uses Brown’s method to combine SNP p-values and account for LD. We used ENSEMBL gene models for 19,079 genes giving a Bonferroni corrected P-value threshold of 2.6×10−6. Gene set P-values were obtained using a competitive analysis that tests whether genes in a gene set are more strongly associated with the phenotype than other gene sets. We used European-ancestry subjects from 1,000 Genomes Project (Phase 3 v5a, MAF ≥ 0.01)101 for the LD reference. The gene window used was 35 kb upstream and 10 kb downstream to include regulatory elements.