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• W4386530946 abstract "BackgroundChronic pain is a common, poorly-understood condition. Genetic studies including genome wide association studies (GWAS) identify many relevant variants, which have yet to be translated into full understanding of chronic pain. Transcriptome wide association study using transcriptomic imputation (TI) methods such as S-PrediXcan can help bridge this genotype-phenotype gap.MethodsWe carried out TI using S-PrediXcan to identify genetically regulated gene expression (GREX) associated with Multisite Chronic Pain (MCP), in thirteen brain tissues and whole blood. We then imputed GREX for over 31,000 Mount Sinai BioMe™ participants and performed phenome-wide association study (PheWAS) to investigate clinical relationships in chronic pain associated gene expression changes.ResultsWe identified 95 experiment-wide significant gene-tissue associations (p<7.97x10-7), including 35 unique genes, and an additional 134 gene-tissue associations reaching within-tissue significance, including 53 additional unique genes. Of 89 unique genes total, 59 were novel for MCP and 18 are established drug targets. Chronic pain GREX for 10 unique genes was significantly associated with cardiac dysrhythmia, metabolic syndrome, disc disorders/ dorsopathies, joint/ligament sprain, anemias, and neurological disorder phecodes. PheWAS analyses adjusting for mean painscore showed associations were not driven by mean painscore.ConclusionsWe carried out the largest TI study of any chronic pain trait to date. Results highlight potential causal genes in chronic pain development, and tissue and direction of effect. Several gene results were also drug targets. PheWAS results showed significant association for phecodes including cardiac dysrhythmia and metabolic syndrome, indicating potential shared mechanisms." @default.
• W4386530946 created "2023-09-09" @default.
• W4386530946 creator A5006025541 @default.
• W4386530946 creator A5033812017 @default.
• W4386530946 creator A5046353227 @default.
• W4386530946 creator A5064089718 @default.
• W4386530946 creator A5089323585 @default.
• W4386530946 date "2023-09-01" @default.
• W4386530946 modified "2023-10-12" @default.
• W4386530946 title "Genetically-regulated gene expression in the brain associated with chronic pain: relationships with clinical traits and potential for drug repurposing" @default.
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