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dc.contributor.authorLai, Dongbing
dc.contributor.authorSchwantes-An, Tae-Hwi
dc.contributor.authorAbreu, Marco
dc.contributor.authorChan, Grace
dc.contributor.authorHesselbrock, Victor
dc.contributor.authorKamarajan, Chella
dc.contributor.authorLiu, Yunlong
dc.contributor.authorMeyers, Jacquelyn L
dc.contributor.authorNurnberger, John I
dc.contributor.authorPlawecki, Martin H
dc.contributor.authorWetherill, Leah
dc.contributor.authorSchuckit, Marc
dc.contributor.authorZhang, Pengyue
dc.contributor.authorEdenberg, Howard J
dc.contributor.authorPorjesz, Bernice
dc.contributor.authorAgrawal, Arpana
dc.contributor.authorForoud, Tatiana
dc.date.accessioned2022-11-16T19:37:45Z
dc.date.available2022-11-16T19:37:45Z
dc.date.issued2022-07-05
dc.identifier.citationLai D, Schwantes-An TH, Abreu M, Chan G, Hesselbrock V, Kamarajan C, Liu Y, Meyers JL, Nurnberger JI Jr, Plawecki MH, Wetherill L, Schuckit M, Zhang P, Edenberg HJ, Porjesz B, Agrawal A, Foroud T. Gene-based polygenic risk scores analysis of alcohol use disorder in African Americans. Transl Psychiatry. 2022 Jul 5;12(1):266. doi: 10.1038/s41398-022-02029-2. PMID: 35790736; PMCID: PMC9256707.en_US
dc.identifier.eissn2158-3188
dc.identifier.doi10.1038/s41398-022-02029-2
dc.identifier.pmid35790736
dc.identifier.urihttp://hdl.handle.net/20.500.12648/7896
dc.description.abstractGenome-wide association studies (GWAS) in admixed populations such as African Americans (AA) have limited sample sizes, resulting in poor performance of polygenic risk scores (PRS). Based on the observations that many disease-causing genes are shared between AA and European ancestry (EA) populations, and some disease-causing variants are located within the boundaries of these genes, we proposed a novel gene-based PRS framework (PRS) by using variants located within disease-associated genes. Using the AA GWAS of alcohol use disorder (AUD) from the Million Veteran Program and the EA GWAS of problematic alcohol use as the discovery GWAS, we identified 858 variants from 410 genes that were AUD-related in both AA and EA. PRS calculated using these variants were significantly associated with AUD in three AA target datasets (P-values ranged from 7.61E-05 to 6.27E-03; Betas ranged from 0.15 to 0.21) and outperformed PRS calculated using all variants (P-values ranged from 7.28E-03 to 0.16; Betas ranged from 0.06 to 0.18). PRS were also associated with AUD in an EA target dataset (P-value = 0.02, Beta = 0.11). In AA, individuals in the highest PRS decile had an odds ratio of 1.76 (95% CI: 1.32-2.34) to develop AUD compared to those in the lowest decile. The 410 genes were enriched in 54 Gene Ontology biological processes, including ethanol oxidation and processes involving the synaptic system, which are known to be AUD-related. In addition, 26 genes were targets of drugs used to treat AUD or other diseases that might be considered for repurposing to treat AUD. Our study demonstrated that the gene-based PRS had improved performance in evaluating AUD risk in AA and provided new insight into AUD genetics.en_US
dc.language.isoenen_US
dc.relation.urlhttps://www.nature.com/articles/s41398-022-02029-2en_US
dc.rights© 2022. The Author(s).
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleGene-based polygenic risk scores analysis of alcohol use disorder in African Americans.en_US
dc.typeArticle/Reviewen_US
dc.source.journaltitleTranslational psychiatryen_US
dc.source.volume12
dc.source.issue1
dc.source.beginpage266
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.description.versionVoRen_US
refterms.dateFOA2022-11-16T19:37:46Z
dc.description.institutionSUNY Downstateen_US
dc.description.departmentHenri Begleiter Neurodynamics Laboratoryen_US
dc.description.degreelevelN/Aen_US
dc.identifier.journalTranslational psychiatry


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