Psychiatry and Medical Genetics, University of Alberta, Edmonton, AB, Canada.
MRC Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK.
Transl Psychiatry. 2018 Aug 13;8(1):150. doi: 10.1038/s41398-018-0198-3.
A key feature of major depressive disorder (MDD) is anhedonia, which is a predictor of response to antidepressant treatment. In order to shed light on its genetic underpinnings, we conducted a genome-wide association study (GWAS) followed by investigation of biological pathway enrichment using an anhedonia dimension for 759 patients with MDD in the GENDEP study. The GWAS identified 18 SNPs associated at genome-wide significance with the top one being an intronic SNP (rs9392549) in PRPF4B (pre-mRNA processing factor 4B) located on chromosome 6 (P = 2.07 × 10) while gene-set enrichment analysis returned one gene ontology term, axon cargo transport (GO: 0008088) with a nominally significant P value (1.15 × 10). Furthermore, our exploratory analysis yielded some interesting, albeit not statistically significant genetic correlation with Parkinson's Disease and nucleus accumbens gray matter. In addition, polygenic risk scores (PRSs) generated from our association analysis were found to be able to predict treatment efficacy of the antidepressants in this study. In conclusion, we found some markers significantly associated with anhedonia, and some suggestive findings of related pathways and biological functions, which could be further investigated in other studies.
重性抑郁障碍（MDD）的一个主要特征是快感缺失，它是抗抑郁治疗反应的预测因子。为了阐明其遗传基础，我们对 GENDEP 研究中的 759 名 MDD 患者进行了全基因组关联研究（GWAS），并对生物途径富集进行了调查，使用快感缺失维度。GWAS 确定了 18 个与全基因组显著相关的 SNP，其中最显著的是位于 6 号染色体上的 PRPF4B（前体 mRNA 处理因子 4B）内含子 SNP（rs9392549）（P=2.07×10），而基因集富集分析返回了一个基因本体术语，轴突货物运输（GO：0008088），具有名义上显著的 P 值（1.15×10）。此外，我们的探索性分析得出了一些有趣的结果，尽管与帕金森病和伏隔核灰质的遗传相关性没有统计学意义。此外，我们从关联分析中生成的多基因风险评分（PRS）被发现能够预测本研究中抗抑郁药的治疗效果。总之，我们发现了一些与快感缺失显著相关的标记，以及一些相关途径和生物学功能的提示性发现，这些发现可以在其他研究中进一步研究。
