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Chunk #69 — STAR★METHODS — QUANTIFICATION AND STATISTICAL ANALYSIS — Expression-based mapping of SNPs — Gene associations based on mapping chromatin profiles of brain tissues and cells

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Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies.
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The gene-based association study for brain tissue-derived chromatin profiles for four tissues (fetal brain paracentral cortex; adult brain – DLPFC), and cells (astrocytes and neurons - human iPSCs) was performed using H-MAGMA v.1.08.52,87 Complementary to TWAS and the coloc approaches, H-MAGMA maps functional and regulatory effects of non-coding SNPs based on three-dimensional chromatin data. We tested all four tissue profiles integrated with GWAS association statistics using European genetic-ancestry reference panels. Bonferroni correction (0.05/number of associations = 3.73× 10−6) on unique genes and four tissues was applied to define significant associations. The genes were grouped into 1Mb regions based on hg19 position; if many genes were within close proximity to each other, then the region size was bigger than 1Mb (e.g. for the MHC region).