The major depressive disorder GWAS-supported variant rs10514299 in TMEM161B-MEF2C predicts putamen activation during reward processing in alcohol dependence

Translational Psychiatry
Christine MuenchFalk W Lohoff

Abstract

Alcohol dependence (AD) frequently co-occurs with major depressive disorder (MDD). While this comorbidity is associated with an increase in disease burden, worse treatment outcomes, and greater economic costs, the underlying neurobiology remains poorly understood. A recent large-scale GWAS of MDD has identified a locus in the TMEM161B-MEF2C region (rs10514299) as a novel risk variant; however, the biological relevance of this variant has not yet been studied. Given previous reports of disrupted reward processing in both AD and MDD, we hypothesized that rs10514299 would be associated with differences in striatal BOLD responses during reward/loss anticipation in AD. DNA samples from 45 recently detoxified patients with AD and 45 healthy controls (HC) were genotyped for rs10514299. Participants performed the Monetary Incentive Delay task in a 3-Tesla MRI scanner. Effects of rs10514299 on striatal activation during anticipation of high/low reward/loss were investigated. Furthermore, we examined associations between rs10514299 and lifetime AD diagnosis in two independent clinical samples [NIAAA: n = 1858 (1123 cases, 735 controls); SAGE: n = 3838 (1848 cases, 1990 controls)], as well as its association with depression severity in a ...Continue Reading

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Citations

Sep 17, 2020·International Journal of Molecular Sciences·Daniel R LathenAdrian Rothenfluh
Aug 23, 2020·Journal of Clinical Medicine·Adriana FarréFrancina Fonseca
Dec 10, 2019·Human Genetics·Sha LiuFuquan Zhang
Feb 19, 2021·Proceedings of the National Academy of Sciences of the United States of America·Charlotte D KoopmanKelly A Smith

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Methods Mentioned

BETA
genotyping

Software Mentioned

SPSS
PLINK
AFNI DrawDataset
AFNI
SPSS Statistics

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