AI Article Synopsis

  • Genetic risks for substance use disorders (SUDs) arise from both specific and shared genes, and researchers conducted extensive analyses across different ancestries to find these shared genes.
  • They discovered 45 loci and identified 250 SUD-shared genes, which are mainly active in key brain areas associated with emotion and memory.
  • The study highlighted that individuals with high polygenic scores are significantly more likely to develop SUDs, with better predictability in females, and also identified potential drug treatments that target these shared genes.

Article Abstract

Genetic risks for substance use disorders (SUDs) are due to both SUD-specific and SUD-shared genes. We performed the largest multivariate analyses to date to search for SUD-shared genes using samples of European (EA), African (AA), and Latino (LA) ancestries. By focusing on variants having cross-SUD and cross-ancestry concordant effects, we identified 45 loci. Through gene-based analyses, gene mapping, and gene prioritization, we identified 250 SUD-shared genes. These genes are highly expressed in amygdala, cortex, hippocampus, hypothalamus, and thalamus, primarily in neuronal cells. Cross-SUD concordant variants explained ~ 50% of the heritability of each SUD in EA. The top 5% individuals having the highest polygenic scores were approximately twice as likely to have SUDs as others in EA and LA. Polygenic scores had higher predictability in females than in males in EA. Using real-world data, we identified five drugs targeting identified SUD-shared genes that may be repurposed to treat SUDs.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11275984PMC
http://dx.doi.org/10.21203/rs.3.rs-3955955/v1DOI Listing

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Article Synopsis
  • Genetic risks for substance use disorders (SUDs) arise from both specific and shared genes, and researchers conducted extensive analyses across different ancestries to find these shared genes.
  • They discovered 45 loci and identified 250 SUD-shared genes, which are mainly active in key brain areas associated with emotion and memory.
  • The study highlighted that individuals with high polygenic scores are significantly more likely to develop SUDs, with better predictability in females, and also identified potential drug treatments that target these shared genes.
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