Kibitov A O, Rakitko A S, Kasyanov E D, Rukavishnikov G V, Shumskaia D S, Ilinsky V V, Neznanov N G, Mazo G E
Bekhterev National Medical Research Center for Psychiatry and Neurology, St. Petersburg, Russia.
Pavlov First Saint-Petersburg State Medical University, St. Petersburg, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(11):122-131. doi: 10.17116/jnevro2024124111122.
To test an associations of online phenotypes of depressive symptoms with polygenic risk scores (PRS) for selected somatic diseases in a population-based cohort.
Participants in a Russian population-based cohort (=4520) underwent online phenotyping based on the originally developed questionnaire using DSM-5 criteria (DSM phenotypes) and the Hospital Anxiety and Depression Scale (HADS) questionnaire (HADS phenotypes). After DNA genotyping with microarrays, PRS were calculated using summary statistics from large-scale GWASs (mostly from UK Biobank) for irritable bowel syndrome (IBS), coronary heart disease (narrow and broad phenotypes) (CHD), ischemic stroke (IS),diabetes mellitus type 2 (DT2) and migraine (MG). Then we assessed associations of PRS for somatic diseases with online phenotypes of depressive symptoms in a population-based cohort.
Highly specific associations of PRS for somatic diseases with online phenotypes of depressive symptoms in a population cohort were identified: positive associations of PRS IBS with «DSM depression» (=0.0035) and PRS CHD (narrow phenotype) with «DSM bipolar disorder» (=0.0207), as well as a negative association of PRS IS with the symptomatic DSM phenotype «Hyperphagia» (=0.0262). All the HADS phenotypes (clinical depression, subclinical depression, and HADS-D total score) showed a positive association with PRS for IBS and DT2, and at the same time were negatively associated with PRS IS. The DSM phenotype «Hypersomnia and hyperphagia» was positively associated with PRS for DT2 and IS, and negatively associated with PRS CHD (narrow phenotype). The DSM phenotypes «Subclinical Depression», «Hypersomnia», and «Anhedonia» showed exclusively negative associations with PRSs for DT2, IS, and IBS. Three maximum informative PRS by explained variance (PRS.R2) were found for the single DSM phenotype «Hypersomnia and hyperphagia»: PRS for IS and DT2 are positively associated and increase the risk of this phenotype, and PRS CHD (narrow phenotype) has a negative association and reduces the risk of this phenotype.
Our study confirmed the presence of possible genetic comorbidity of depression and chronic somatic diseases and showed different effectiveness of online phenotyping of depressive symptoms as markers of genetic risk of somatic diseases in the population cohort. Further research is needed to construct various versions of online phenotyping test systems for population-based screening of cohorts at high genetic risk for genetically comorbid diseases.
在一项基于人群的队列研究中，测试抑郁症状的在线表型与特定躯体疾病的多基因风险评分（PRS）之间的关联。
俄罗斯一项基于人群的队列研究（n = 4520）的参与者，根据最初开发的问卷，采用DSM-5标准（DSM表型）和医院焦虑抑郁量表（HADS）问卷（HADS表型）进行在线表型分析。在使用微阵列进行DNA基因分型后，利用来自大规模全基因组关联研究（GWAS）（主要来自英国生物银行）的汇总统计数据，计算肠易激综合征（IBS）、冠心病（狭义和广义表型）（CHD）、缺血性中风（IS）、2型糖尿病（DT2）和偏头痛（MG）的PRS。然后，我们在基于人群的队列中评估躯体疾病的PRS与抑郁症状在线表型之间的关联。
在人群队列中，确定了躯体疾病的PRS与抑郁症状在线表型之间高度特异性的关联：PRS IBS与“DSM抑郁”呈正相关（P = 0.0035），PRS CHD（狭义表型）与“DSM双相情感障碍”呈正相关（P = 0.0207），以及PRS IS与有症状的DSM表型“食欲亢进”呈负相关（P = 0.0262）。所有HADS表型（临床抑郁、亚临床抑郁和HADS-D总分）与IBS和DT2的PRS呈正相关，同时与PRS IS呈负相关。DSM表型“嗜睡和食欲亢进”与DT2和IS的PRS呈正相关，与PRS CHD（狭义表型）呈负相关。DSM表型“亚临床抑郁”、“嗜睡”和“快感缺失”仅与DT2、IS和IBS的PRS呈负相关。对于单一的DSM表型“嗜睡和食欲亢进”，通过解释方差（PRS.R2）发现了三个信息量最大的PRS：IS和DT2的PRS呈正相关，增加了该表型的风险，而PRS CHD（狭义表型）呈负相关，降低了该表型的风险。
我们的研究证实了抑郁症与慢性躯体疾病可能存在遗传共病，并表明抑郁症状在线表型作为人群队列中躯体疾病遗传风险标志物的不同有效性。需要进一步研究构建各种版本的在线表型测试系统，用于对具有遗传共病高风险的人群队列进行基于人群的筛查。
