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• W3091794330 abstract "Abstract Twin studies indicate that there is a significant genetic contribution to the risk of developing alcohol use disorder (AUD). With the exception of coding variants in ADH1B and ALDH2 , little is known about the molecular effects of AUD‐associated loci. We previously reported that the AUD‐associated synonymous polymorphism rs279858 within the GABA A α2 receptor subunit gene, GABRA2 , was associated with gene expression of the chr4p12 GABA A subunit gene cluster in induced pluripotent stem cell (iPSC)‐derived neural cultures. Based on this and other studies that showed changes in GABRA2 DNA methylation associated with schizophrenia and aging, we examined methylation in GABRA2 . Specifically, using 69 iPSC lines and neural cultures derived from 47 of them, we examined whether GABRA2 rs279858 genotype predicted methylation levels and whether methylation was related to GABA A receptor subunit gene expression. We found that the GABRA2 CpG island undergoes random stochastic methylation during reprogramming and that methylation is associated with decreased GABRA2 gene expression, an effect that extends to the GABRB1 gene over 600 kb distal to GABRA2 . Further, we identified additive effects of GABRA2 CpG methylation and GABRA2 rs279858 genotype on expression of the GABRB1 subunit gene in iPSC‐derived neural cultures." @default.
• W3091794330 created "2020-10-15" @default.
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• W3091794330 date "2020-10-07" @default.
• W3091794330 modified "2023-10-10" @default.
• W3091794330 title "Induced pluripotent stem cell reprogramming‐associated methylation at the <scp><i>GABRA2</i></scp> promoter and chr4p12 <scp>GABA_A</scp> subunit gene expression in the context of alcohol use disorder" @default.
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• W3091794330 doi "https://doi.org/10.1002/ajmg.b.32824" @default.
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