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Chunk #58 — Methods — MAGMA gene-based and gene-set analyses

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Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.
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Gene-based association analyses were conducted using MAGMA31 v1.08. SNPs were positionally mapped (0-kb window) to 19,106 protein-coding genes. The SNP-wide mean model was used to derive gene-level P-values, with an ancestry appropriate KGP3 reference panel was used to model LD. Significance was declared based on Bonferroni adjustment for the number of genes tested. Gene-based association statistics were used in MAGMA for gene-set and gene-property analyses. Gene-set analysis used the MsigDB33 version 7.0 including 15,483 curated gene-sets and gene-ontology (GO) terms. Gene-property analysis of tissues and tissue subtypes was performed using GTEx v8 expression data, with adjustment for the average expression of all tissues in the dataset. To evaluate cell type specific enrichment, the FUMA cell type module was used, selecting 12 datasets related to the brain (full list in Supplementary Note). Finally, MAGMA was used to estimate the enrichment of dlPFC cell types in PTSD risk based on the DER21 marker gene list from PsychEncode Consortium Phase 1 resource release102.