Honghuang Lin1,2, Fan Wang3, Andrew J Rosato4, Lindsay A Farrer5, David C Henderson4, Huiping Zhang4,5. 1. Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, MA, USA. 2. Boston University's & National Heart, Lung & Blood Institute's Framingham Heart Study, MA, USA. 3. Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic Lerner Research Institute, OH, USA. 4. Department of Psychiatry, Boston University School of Medicine, MA, USA. 5. Section of Biomedical Genetics, Department of Medicine, Boston University School of Medicine, MA, USA.
Abstract
Aim: This study aimed to investigate the function of genome-wide association study (GWAS)-identified variants associated with alcohol use disorder (AUD)/comorbid psychiatric disorders. Materials & methods: Genome-wide genotype, transcriptome and DNA methylome data were obtained from postmortem prefrontal cortex (PFC) of 48 Caucasians (24 AUD cases/24 controls). Expression/methylation quantitative trait loci (eQTL/mQTL) were identified and their enrichment in GWAS signals for the above disorders were analyzed. Results: PFC cis-eQTLs (923 from cases+controls, 27 from cases and 98 from controls) and cis-mQTLs (9,932 from cases+controls, 264 from cases and 695 from controls) were enriched in GWAS-identified genetic variants for the above disorders. Cis-eQTLs from AUD cases were mapped to morphine addiction-related genes. Conclusion: PFC cis-eQTLs/cis-mQTLs influence gene expression/DNA methylation patterns, thus increasing the disease risk.
Aim: This study aimed to investigate the function of genome-wide association study (GWAS)-identified variants associated with alcohol use disorder (AUD)/comorbid psychiatric disorders. Materials & methods: Genome-wide genotype, transcriptome and DNA methylome data were obtained from postmortem prefrontal cortex (PFC) of 48 Caucasians (24 AUD cases/24 controls). Expression/methylation quantitative trait loci (eQTL/mQTL) were identified and their enrichment in GWAS signals for the above disorders were analyzed. Results: PFC cis-eQTLs (923 from cases+controls, 27 from cases and 98 from controls) and cis-mQTLs (9,932 from cases+controls, 264 from cases and 695 from controls) were enriched in GWAS-identified genetic variants for the above disorders. Cis-eQTLs from AUD cases were mapped to morphine addiction-related genes. Conclusion: PFC cis-eQTLs/cis-mQTLs influence gene expression/DNA methylation patterns, thus increasing the disease risk.
Entities:
Keywords:
alcohol use disorder; enrichment analysis; expression quantitative trait loci; genome-wide association study; human prefrontal cortex; methylation quantitative trait loci
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