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Chunk #62 — STAR* METHODS — QUANTIFICATION AND STATISTICAL ANALYSIS — Functional annotation and gene-mapping of genome-wide significant variants

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Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders.
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For the 146 genome-wide significant variants, gene mapping and functional annotation was conducted using various resources, including SNPNexus (Dayem et al., 2018) and FUMA (Watanabe et al., 2017). Nearest genes and functional consequence of each SNP on gene functions were annotated based on ANNOVAR (Wang et al., 2010). Combined Annotation Dependent Depletion (CADD) score (Kircher, 2014) indexes the deleteriousness of variants computed based on 67 annotation resources. SNPs with the CADD score higher than 12 were considered to confer deleterious effects. The RegulomeDB (Boyle, 2012) provides a categorical score that describes how likely a SNP is likely to play a regulatory role based on the integration of high-throughput datasets. The RDB score of 1a suggests the strongest evidence, while the score 7 represents the least support for a regulatory potential. The minChrState and the commonChrState represent the minimum and the most common15-core chromatin state across 127 tissue/cell type predicted by ChrHMM. The chromatin state of less than 8 suggests an open chromatin state. eQTL mapping provides significant cis-SNP-gene pairs (up to 1Mb apart) in brain tissue types from GTEx and BRAINEAC.