UNASSIGNED: We constructed a polysocial risk score (PsRS), a multidimensional social risk indicator including components from three domains: socioeconomic status, neighborhood and living environment and psychosocial factors. Supported by the UK Biobank cohort, we randomly divided 110 332 participants into the discovery cohort (60%; n = 66 200) and the replication cohort (40%; n = 44 134). We tested the associations between 13 single social factors with Patient Health Questionnaire (PHQ) score, Generalized Anxiety Disorder Scale (GAD) score and self-reported depression and anxiety. The significant social factors were used to calculate PsRS for each mental disorder by considering weights from the multivariable linear model. Generalized linear models were applied to explore the association between PsRS and depression and anxiety. Genome-wide environmental interaction study (GWEIS) was further performed to test the effect of interactions between PsRS and SNPs on the risk of mental phenotypes.
UNASSIGNED: In the discovery cohort, PsRS was positively associated with PHQ score (β = 0.37; 95% CI = 0.35-0.38), GAD score (β = 0.27; 95% CI = 0.25-0.28), risk of self-reported depression (OR = 1.29; 95% CI = 1.28-1.31) and anxiety (OR = 1.19; 95% CI = 1.19-1.23). Similar results were observed in the replication cohort. Emotional stress, lack of social support and low household income were significantly associated with the development of depression and anxiety. GWEIS identified multiple candidate loci for PHQ score, such as rs149137169 (ST18) (Pdiscovery = 1.08 × 10-8, Preplication = 3.25 × 10-6) and rs3759812 (MYO9A) (Pdiscovery = 3.87 × 10-9, Preplication = 6.21 × 10-5). Additionally, seven loci were detected for GAD score, such as rs114006170 (TMPRSS11D) (Pdiscovery = 1.14 × 10-9, Preplication = 7.36 × 10-5) and rs77927903 (PIP4K2A) (Pdiscovery = 2.40 × 10-9, Preplication = 0.002).
UNASSIGNED: Our findings reveal the positive effects of multidimensional social factors on the risk of depression and anxiety. It is important to address key social disadvantage in mental health promotion and treatment.
■我们构建了一个多社会风险评分(PsRS),一个多维社会风险指标,包括来自三个领域的组成部分:社会经济地位,邻里、生活环境和社会心理因素。在英国生物银行队列的支持下,我们将110332名参与者随机分为发现队列(60%;n=66200)和复制队列(40%;n=44134).我们测试了13个单一社会因素与患者健康问卷(PHQ)得分之间的关联,广义焦虑症量表(GAD)评分及自我报告抑郁和焦虑。通过考虑多变量线性模型的权重,使用重要的社会因素来计算每种精神障碍的PsRS。应用广义线性模型探讨PsRS与抑郁和焦虑之间的关系。进一步进行全基因组环境相互作用研究(GWEIS)以测试PsRS和SNP之间的相互作用对精神表型风险的影响。
■在发现队列中,PsRS与PHQ评分呈正相关(β=0.37;95%CI=0.35-0.38),GAD评分(β=0.27;95%CI=0.25-0.28),自我报告抑郁(OR=1.29;95%CI=1.28-1.31)和焦虑(OR=1.19;95%CI=1.19-1.23)的风险.在复制队列中观察到类似的结果。情绪紧张,缺乏社会支持和低家庭收入与抑郁和焦虑的发展显著相关。GWEIS确定了PHQ得分的多个候选基因座,例如rs149137169(ST18)(Pdiscovery=1.08×10-8,Prepplication=3.25×10-6)和rs3759812(MYO9A)(Pdiscovery=3.87×10-9,Prepplication=6.21×10-5)。此外,检测到7个位点的GAD评分,例如rs114006170(TMPRSS11D)(Pdiscovery=1.14×10-9,Prepplication=7.36×10-5)和rs77927903(PIP4K2A)(Pdiscovery=2.40×10-9,Prepplication=0.002)。
■我们的发现揭示了多维社会因素对抑郁和焦虑风险的积极影响。重要的是要解决心理健康促进和治疗中的关键社会不利因素。