Browsing by Subject "Substance use disorders (SUDs)"

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    Clinical, environmental, and genetic risk factors for substance use disorders: characterizing combined effects across multiple cohorts
    (Springer, 2022-10-04) Barr, Peter B.; Driver, Morgan N.; Kuo, Sally I-Chun; Stephenson, Mallory; Aliev, Fazil; Linnér, Richard Karlsson; Marks, Jesse; Anokhin, Andrey P.; Bucholz, Kathleen; Chan, Grace; Edenberg, Howard J.; Edwards, Alexis C.; Francis, Meredith W.; Hancock, Dana B.; Harden, K. Paige; Kamarajan, Chella; Kaprio, Jaakko; Kinreich, Sivan; Kramer, John R.; Kuperman, Samuel; Latvala, Antti; Meyers, Jacquelyn L.; Palmer, Abraham A.; Plawecki, Martin H.; Porjesz, Bernice; Rose, Richard J.; Schuckit, Marc A.; Salvatore, Jessica E.; Dick , Danielle M.; Medical and Molecular Genetics, School of Medicine
    Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.
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    Genome-wide meta-analyses of cross substance use disorders in European, African, and Latino ancestry populations
    (Research Square, 2024-07-16) Lai, Dongbing; Zhang, Michael; Green, Nick; Abreu, Marco; Schwantes-An, Tae-Hwi; Parker, Clarissa; Zhang, Shanshan; Jin, Fulai; Sun, Anna; Zhang, Pengyue; Edenberg, Howard; Liu, Yunlong; Foroud, Tatiana; Medical and Molecular Genetics, School of Medicine
    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.