Ye Jing, Wen Yan, Chu Xiaomeng, Li Ping, Cheng Bolun, Cheng Shiqiang, Liu Li, Zhang Lu, Ma Mei, Qi Xin, Liang Chujun, Kafle Om Prakash, Jia Yumeng, Wu Cuiyan, Wang Sen, Wang Xi, Ning Yujie, Zhang Feng
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
Clin Transl Med. 2020 Jun;10(2):e108. doi: 10.1002/ctm2.108. Epub 2020 Jun 20.
Herpes simplex virus-1 (HSV-1) infection is reported to be associated with depression. But limited efforts were made to investigate the relationship between HSV-1 infection and the risk of depression, especially from the genetic perspective.
In UK Biobank cohort, linear and logistic regression analyses were first performed to test the association of HSV-1 seropositivity/antibody with depression, including depression status (N = 2951) and Patient Health Questionnaire (PHQ) score (N = 2839). Using individual genotypic and phenotypic data from the UK Biobank, genome-wide environmental interaction study (GWEIS) was then conducted by PLINK2.0 to evaluate gene × HSV-1 interacting effect on the risk of depression. Finally, gene set enrichment analysis was conducted to identify the biological pathways involved in the observed gene × HSV-1 interaction for depression.
In UK Biobank cohort, significant associations were observed between depression status and HSV-1 (odds ratio [OR] = 1.09; 95% confidence interval [CI], 1.02-1.16; P = 2.40 × 10 for HSV-1 antibody and OR = 1.28; 95% CI, 1.12-1.47, P = 2.59 × 10 for HSV-1 seropositivity). GWEIS revealed four significant gene × HSV-1 interaction signals for PHQ score (all P < 5.0 × 10 ) and the leading loci was SULF2 (rs6094791, P = 8.60 × 10 ). Pathway analyses identified 21 pathways for PHQ score and 19 for depression status, including multiple neural development- and immune-related ones, such as KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION (false discovery rate [FDR] = 3.18 × 10 ) for depression and LU_AGING_BRAIN_UP (FDR = 4.21 × 10 ) for PHQ score.
Our results suggested that HSV-1 was associated with the risk of depression, which was modulated by the several genes that were related to the nerve development or immune function.
据报道，单纯疱疹病毒1型（HSV-1）感染与抑郁症有关。但对于HSV-1感染与抑郁症风险之间的关系，尤其是从遗传学角度进行的研究较少。
在英国生物银行队列中，首先进行线性和逻辑回归分析，以检验HSV-1血清阳性/抗体与抑郁症之间的关联，包括抑郁状态（N = 2951）和患者健康问卷（PHQ）评分（N = 2839）。然后使用来自英国生物银行的个体基因型和表型数据，通过PLINK2.0进行全基因组环境相互作用研究（GWEIS），以评估基因×HSV-1对抑郁症风险的相互作用效应。最后，进行基因集富集分析，以确定观察到的基因×HSV-1相互作用中涉及抑郁症的生物学途径。
在英国生物银行队列中，观察到抑郁状态与HSV-1之间存在显著关联（HSV-1抗体的优势比[OR] = 1.09；95%置信区间[CI]，1.02 - 1.16；P = 2.40×10；HSV-1血清阳性的OR = 1.28；95% CI，1.12 - 1.47，P = 2.59×10）。GWEIS揭示了4个与PHQ评分显著相关的基因×HSV-1相互作用信号（所有P < 5.0×10），主要位点是SULF2（rs6094791，P = 8.60×10）。通路分析确定了21条与PHQ评分相关的通路和19条与抑郁状态相关的通路，包括多个与神经发育和免疫相关的通路，如抑郁的KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION（错误发现率[FDR] = 3.18×10）和PHQ评分的LU_AGING_BRAIN_UP（FDR = 4.21×10）。
我们的结果表明，HSV-1与抑郁症风险相关，这受到几个与神经发育或免疫功能相关的基因的调节。
