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. 2020 May;12(9):789-800.
doi: 10.2217/epi-2019-0270. Epub 2020 Jun 4.

Prefrontal cortex eQTLs/mQTLs enriched in genetic variants associated with alcohol use disorder and other diseases

Honghuang Lin  1   2 , Fan Wang  3 , Andrew J Rosato  4 , Lindsay A Farrer  5 , David C Henderson  4 , Huiping Zhang  4   5
Affiliations

Prefrontal cortex eQTLs/mQTLs enriched in genetic variants associated with alcohol use disorder and other diseases

Honghuang Lin et al. Epigenomics. 2020 May.

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.

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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Conflict of interest statement

Financial & competing interests disclosure

This work was supported by grants (R01AA025080 [H Zhang] and R21AA023068 [H Zhang]) from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.
Figure 1.. Proportions of expression quantitative trait loci shared between the prefrontal cortex and 48 different tissues included in the Genotype-Tissue Expression database.
EBV: Epstein–Barr virus; eQTL: Expression quantitative trait locus; PFC: Prefrontal cortex.
See this image and copyright information in PMC

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