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    • 44. GENOME-WIDE ASSOCIATION META-ANALYSIS OF ANXIETY SYMPTOMS IN 493,764 INDIVIDUALS

    Megan Skelton,Brittany Mitchell,Elham Assary,Danyang Li,Genevieve Morneau-Vaillancourt,Abigail ter Kuile, Rujia Wang,Catharina Hartman,Nicholas G. Martin,Gerome Breen,Jonathan Coleman,John Hettema,Thalia Eley

    European Neuropsychopharmacology（2024）

    Institute of Psychiatry | QIMR Berghofer Medical Research Institute | School of Criminology | University College London | University of Groningen | Texas A and M University

    Cited 0|Views6
    Abstract
    Background Anxiety rates have been climbing over the past two decades, with primary care services reporting record highs. Clinical anxiety is highly burdensome and disabling, and elevated anxiety symptoms are observed across a range of psychiatric disorders. Despite this, anxiety has been understudied in comparison with other psychiatric disorders. As such, genomic discovery for anxiety lags behind that of the other most common mental health disorder, depression. Here, we present preliminary results from the PGC Anxiety Disorders Working Group (PGC-ANX) dimensional anxiety meta-analysis in the largest sample to date. Given evidence of high genetic correlations between individual differences in current anxiety symptoms across the population and lifetime anxiety disorder (1,2), we take this approach to maximise power for genetic discovery. Methods The first freeze consists of 493,764 participants from 9 cohorts. Most participants were phenotyped using the GAD-7 questionnaire, a measure of recent anxiety symptoms. Summary statistics from each genome-wide association analysis were meta-analysed using METAL. SNP-based heritability and genetic correlations with a range of traits were estimated via LDSC. Possible differences between population-based and clinical cohorts, as well as between anxiety symptom measures, will be examined through genetic correlations and where possible genomic SEM. We will also perform leave-one-cohort-out polygenic scoring as well as gene-based associations, gene-set and tissue expression analyses. Results We identified 47 genome-wide significant loci in the meta-analysis. SNP heritability was estimated as 5.5% (95% CI 5.0%-6.0%). Strong genetic correlations were estimated with Major Depressive Disorder, depression symptoms, neuroticism, tiredness and loneliness (rg .70 to .88), and moderate correlations with a wide array of phenotypes from age at first birth and verbal-numerical reasoning to childhood maltreatment and self-rated health (absolute rg .30-.57). Discussion Meta-analysis of anxiety symptoms in nearly half a million participants revealed 47 significant genetic loci and found expected genetic correlations with other phenotypes. More diverse samples are urgently necessary to advance this analysis; we are eager to hear from any research groups with dimensional anxiety measures in genotyped samples of other ancestries.1.Levey, D. F. et al. Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program. Am. J. Psychiatry 177, 223–232 (2020).2.Purves, K. L. et al. A major role for common genetic variation in anxiety disorders. Mol. Psychiatry 25, 3292–3303 (2020). Disclosure Nothing to disclose.
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    【要点】：本研究通过对493,764名个体的焦虑症状进行全基因组关联荟萃分析，发现了47个与焦虑症状显著相关的基因位点，并发现了焦虑症状与其他多种表型之间的遗传相关性。
    

    【方法】：研究使用了9个队列的参与者数据，大部分参与者通过GAD-7问卷进行表型评估，采用METAL软件进行基因组关联分析的汇总统计，使用LDSC估计SNP基础遗传率和与其他表型的遗传相关性。
    

    【实验】：在最大样本量的焦虑症状维度分析中，通过荟萃分析识别了47个基因组广泛显著位点，SNP遗传率估计为5.5%，并与重大抑郁症、抑郁症状、神经过敏、疲劳和孤独等表型表现出强烈的遗传相关性，与其他多种表型表现出中度相关性。数据来源于9个不同队列，具体数据集名称未在摘要中提及。