期刊
EPIGENOMICS
卷 12, 期 9, 页码 789-800出版社
FUTURE MEDICINE LTD
DOI: 10.2217/epi-2019-0270
关键词
alcohol use disorder; enrichment analysis; expression quantitative trait loci; genome-wide association study; human prefrontal cortex; methylation quantitative trait loci
资金
- National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01AA025080, R21AA023068]
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.
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