Huang Lianyun, Tang Sonja, Rietkerk Jolien, Appadurai Vivek, Krebs Morten Dybdahl, Schork Andrew J, Werge Thomas, Zuber Verena, Kendler Kenneth, Cai Na
Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany.
Computational Health Centre, Helmholtz Zentrum München, Neuherberg, Germany.
medRxiv. 2023 Mar 1:2023.02.27.23286527. doi: 10.1101/2023.02.27.23286527.
Symptoms of Major Depressive Disorder (MDD) are commonly assessed using self-rating instruments like the Patient Health Questionnaire 9 (PHQ9, for current symptoms), and the Composite International Diagnostic Interview Short-Form (CIDI-SF, for lifetime worst-episode symptoms). Using data from the UKBiobank, we show that corresponding symptoms endorsed through PHQ9 and CIDI-SF have low to moderate genetic correlations (rG=0.43-0.87), and this cannot be fully attributed to different severity thresholds or the use of a skip-structure in CIDI-SF. Through a combination of Mendelian Randomization (MR) and polygenic prediction analyses, we find that PHQ9 symptoms are more associated with traits which reflect general dysphoria, while the skip-structure in CIDI-SF allows for the identification of heterogeneity among likely MDD cases. This has important implications on factor analyses performed on their respective genetic covariance matrices for the purpose of identification of genetic factors behind MDD symptom dimensions and heterogeneity.
重度抑郁症（MDD）的症状通常使用自评工具进行评估，如患者健康问卷9（PHQ9，用于评估当前症状）和综合国际诊断访谈简表（CIDI-SF，用于评估终生最严重发作症状）。利用英国生物银行的数据，我们发现通过PHQ9和CIDI-SF认可的相应症状具有低到中等的遗传相关性（rG = 0.43 - 0.87），这不能完全归因于不同的严重程度阈值或CIDI-SF中使用的跳过结构。通过孟德尔随机化（MR）和多基因预测分析相结合，我们发现PHQ9症状与反映一般烦躁情绪的特征更相关，而CIDI-SF中的跳过结构允许识别可能的MDD病例中的异质性。这对于在各自的遗传协方差矩阵上进行因子分析以识别MDD症状维度和异质性背后的遗传因素具有重要意义。
