Skelton Megan, Mundy Jessica, Ter Kuile Abigail R, Adey Brett N, Armour Chérie, Buckman Joshua E J, Coleman Jonathan R I, Davies Molly R, Hirsch Colette R, Hotopf Matthew, Jones Ian R, Kalsi Gursharan, Krebs Georgina, Lee Sang Hyuck, Lin Yuhao, McIntosh Andrew M, Peel Alicia J, Rayner Christopher, Rimes Katharine A, Smith Daniel J, Thompson Katherine N, Veale David, Walters James T R, Hübel Christopher, Breen Gerome, Eley Thalia C
Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.
Psychol Med. 2025 Aug 5;55:e224. doi: 10.1017/S0033291725101037.
Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
The phenotypic correlations were moderate across the three measures (Pearson's = 0.50-0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [] = 0.11-0.19) with high genetic correlations between them ( = 0.79-0.87).
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
日常活动中的功能损害，如工作和社交方面，是重度抑郁症和大多数焦虑症诊断标准的一部分。尽管有证据表明症状严重程度和功能损害部分不同，但功能损害常常被忽视。为了评估功能损害是否能捕捉到超出症状之外的与诊断相关的遗传易感性，我们旨在估计当前抑郁症状、焦虑症状和功能损害的关键指标的遗传度以及它们之间的遗传相关性。
在来自焦虑与抑郁的遗传联系（GLAD）研究的17130名有终生抑郁或焦虑的个体中，我们分析了患者健康问卷-9（抑郁症状）、广泛性焦虑障碍-7（焦虑症状）和工作与社会适应量表（功能损害）的总分。使用REGENIE进行全基因组关联分析。使用GCTA-GREML估计遗传度，并使用双变量GREML估计遗传相关性。
这三项指标之间的表型相关性中等（皮尔逊相关系数=0.50-0.69）。发现所有三个量表都受到低但显著的遗传影响（基于单核苷酸多态性的遗传度[]=0.11-0.19），它们之间的遗传相关性很高（=0.79-0.87）。
在GLAD研究中有终生抑郁或焦虑的个体中，构成症状严重程度基础的基因变异与影响功能损害的基因变异在很大程度上重叠。这表明自我报告的功能损害虽然在临床诊断和治疗结果方面具有相关性，但并不反映出超出基于抑郁或焦虑症状测量所捕捉到的大量额外遗传易感性。
