A genome-wide association study identifies candidate genes for sleep disturbances in depressed individuals.

IF 3.8 3区医学 Q2 GENETICS & HEREDITY

Human Genomics Pub Date : 2024-05-22 DOI:10.1186/s40246-024-00609-5

Xuena Yang, Bolun Cheng, Shiqiang Cheng, Li Liu, Chuyu Pan, Peilin Meng, Chun'e Li, Yujing Chen, Jingxi Zhang, Huijie Zhang, Zhen Zhang, Yan Wen, Yumeng Jia, Huan Liu, Feng Zhang

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引用次数: 0

Abstract

Objective: This study aimed to identify candidate loci and genes related to sleep disturbances in depressed individuals and clarify the co-occurrence of sleep disturbances and depression from the genetic perspective.

Methods: The study subjects (including 58,256 self-reported depressed individuals and 6,576 participants with PHQ-9 score ≥ 10, respectively) were collected from the UK Biobank, which were determined based on the Patient Health Questionnaire (PHQ-9) and self-reported depression status, respectively. Sleep related traits included chronotype, insomnia, snoring and daytime dozing. Genome-wide association studies (GWASs) of sleep related traits in depressed individuals were conducted by PLINK 2.0 adjusting age, sex, Townsend deprivation index and 10 principal components as covariates. The CAUSALdb database was used to explore the mental traits associated with the candidate genes identified by the GWAS.

Results: GWAS detected 15 loci significantly associated with chronotype in the subjects with self-reported depression, such as rs12736689 at RNASEL (P = 1.00 × 10^- 09), rs509476 at RGS16 (P = 1.58 × 10^- 09) and rs1006751 at RFX4 (P = 1.54 × 10^- 08). 9 candidate loci were identified in the subjects with PHQ-9 ≥ 10, of which 2 loci were associated with insomnia such as rs115379847 at EVC2 (P = 3.50 × 10^- 08), and 7 loci were associated with daytime dozing, such as rs140876133 at SMYD3 (P = 3.88 × 10^- 08) and rs139156969 at ROBO2 (P = 3.58 × 10^- 08). Multiple identified genes, such as RNASEL, RGS16, RFX4 and ROBO2 were reported to be associated with chronotype, depression or cognition in previous studies.

Conclusion: Our study identified several candidate genes related to sleep disturbances in depressed individuals, which provided new clues for understanding the biological mechanism underlying the co-occurrence of depression and sleep disorders.

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一项全基因组关联研究发现了抑郁症患者睡眠障碍的候选基因。

研究目的本研究旨在确定与抑郁症患者睡眠障碍相关的候选位点和基因，并从遗传学角度阐明睡眠障碍与抑郁症的共存性：研究对象（包括58256名自我报告的抑郁症患者和6576名PHQ-9评分≥10分的参与者）来自英国生物库，分别根据患者健康问卷（PHQ-9）和自我报告的抑郁状态确定。与睡眠相关的特征包括慢性型、失眠、打鼾和白天打瞌睡。通过 PLINK 2.0 对年龄、性别、汤森剥夺指数和 10 个主成分作为协变量进行调整后，对抑郁症患者的睡眠相关特征进行了全基因组关联研究（GWAS）。CAUSALdb 数据库用于探索与 GWAS 发现的候选基因相关的精神特质：GWAS在自述抑郁的受试者中发现了15个与时间型显著相关的位点，如RNASEL的rs12736689（P = 1.00 × 10-09）、RGS16的rs509476（P = 1.58 × 10-09）和RFX4的rs1006751（P = 1.54 × 10-08）。在PHQ-9≥10的受试者中发现了9个候选位点，其中2个位点与失眠相关，如EVC2的rs115379847（P = 3.50 × 10-08），7个位点与白天打瞌睡相关，如SMYD3的rs140876133（P = 3.88 × 10-08）和ROBO2的rs139156969（P = 3.58 × 10-08）。在以往的研究中，RNASEL、RGS16、RFX4和ROBO2等多个已确定的基因被报道与时型、抑郁或认知相关：我们的研究发现了多个与抑郁症患者睡眠障碍相关的候选基因，为了解抑郁症和睡眠障碍并存的生物学机制提供了新线索。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Genomics GENETICS & HEREDITY-

CiteScore

6.00

自引率

2.20%

发文量

审稿时长

11 weeks

期刊介绍： Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.