Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, 710061, PR China.
Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, 710061, PR China.
Prog Neuropsychopharmacol Biol Psychiatry. 2023 Aug 30;126:110781. doi: 10.1016/j.pnpbp.2023.110781. Epub 2023 May 9.
Previous genetic studies of anxiety and depression were mostly based on independent phenotypes. This study aims to investigate the shared and specific genetic structure between anxiety and depression.
To identify the underlying factors of Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and their combined scale (joint scale), we employed exploratory factor analysis (EFA) using the eigenvalue of parallel analysis. Subsequently, we conducted a genome-wide association study (GWAS) for these factors. In addition, we utilized LD Score Regression (LDSC) to determine the genetic correlations between the identified factors and four common mental disorders, three sleep phenotypes, and other traits that have been previously linked to anxiety and depression.
The EFA uncovered two factors for the GAD-7 scale, namely nervousness and disturbance, two factors for the PHQ-9 scale, namely negative affect and sleep/appetite disturbance, and four factors for the joint scale, specifically nervousness, anhedonia, sleep/appetite disturbance, and fidget. We identified two genome-wide significant genomic loci, with overlap across GAD-7 factor 1 and joint scale factor 1: rs148579586 (P = 1.365 × 10, P = 1.434 × 10) and rs201074060 (P = 3.672 × 10, P = 3.824 × 10). Genetic correlations in factors ranged from 0.722 to 1.000 (all p < 1.786 × 10) with 27 of 28 correlations being significantly smaller than one. The genetic correlations with external phenotypes showed small variation across the eight factors.
Unidimensional structures can provide more precise scores, which can aid in identifying the shared and specific genetic associations between anxiety and depression. This is a crucial step in characterizing the genetic structure of these conditions and their co-occurrence.
之前关于焦虑和抑郁的遗传研究大多基于独立的表型。本研究旨在探讨焦虑和抑郁之间的共同和特定遗传结构。
为了确定广泛性焦虑障碍-7 项量表（GAD-7）、患者健康问卷-9 项量表（PHQ-9）及其联合量表的潜在因素，我们采用平行分析的特征值进行探索性因子分析（EFA）。随后，我们对这些因素进行全基因组关联研究（GWAS）。此外，我们利用 LD 得分回归（LDSC）来确定所确定因素与四种常见精神障碍、三种睡眠表型以及与焦虑和抑郁相关的其他特征之间的遗传相关性。
EFA 揭示了 GAD-7 量表的两个因素，即紧张和紊乱，PHQ-9 量表的两个因素，即负性情绪和睡眠/食欲紊乱，以及联合量表的四个因素，分别是紧张、快感缺失、睡眠/食欲紊乱和烦躁不安。我们确定了两个全基因组显著的基因组位置，跨越 GAD-7 因子 1 和联合量表因子 1 存在重叠：rs148579586（P=1.365×10，P=1.434×10）和 rs201074060（P=3.672×10，P=3.824×10）。因子之间的遗传相关性在 0.722 到 1.000 之间（所有 p 值均小于 1.786×10），28 个相关性中有 27 个显著小于 1。与外部表型的遗传相关性在八个因子之间变化很小。
单一维度结构可以提供更精确的评分，有助于识别焦虑和抑郁之间的共同和特定遗传关联。这是描述这些疾病遗传结构及其共病的关键步骤。
