Genome-wide analyses of quantitative generalised anxiety symptom severity

作者：Megan Skelton, Brittany L. Mitchell, Elham Assary, Danyang Li, Geneviève Morneau‐Vaillancourt, Alan E Murphy, Abigail ter Kuile, Rujia Wang, Mark J. Adams, Enda M. Byrne, Elizabeth C. Corfield, P Grimes, Laurie J. Hannigan, Jihua Hu, Kadri Kõiv, Alex S. F. Kwong, Sergi Papiol, Johanne Hagen Pettersen, Giorgio Pistis, Enrique Castelao, Nora I. Strom, Peter J. van der Most, GLAD+ authors, Lifelines Cohort Study, NIHR Bioresource, Ole A. Andreassen, Angelika Erhardt, Alexandra Havdahl, Nathan Skene, Brad Verhulst, Heike Weber, Chérie Armour, Helga Ask, William Copeland, Udo Dannlowski, Jürgen Deckert, Katharina Domschke, Ian B. Hickie, Kelli Lehto, Tina B. Lonsdorf, Ulrike Lueken, Michelle K. Lupton, Sarah E. Medland, Andrew M. McIntosh, Albertine J. Oldehinkel, Martin Preisig, Andreas Reif, Harold Snieder, James Walters, Naomi R. Wray, Catharina A. Hartman, Nicholas G. Martin, John M. Hettema, Gerome Breen, Jonathan R. I. Coleman, Thalia C. Eley · 发表于：medRxiv · 年份：2025 · DOI：10.1101/2025.07.10.25331321 · 被引用次数：2 · 研究领域：Child and Adolescent Psychosocial and Emotional Development、Tryptophan and brain disorders

We performed a genome-wide association meta-analysis of generalised anxiety symptom severity in 696,563 individuals of European ancestry from 14 cohorts. We identified 82 independent genome-wide significant variants within 76 loci, 41 of which were novel for anxiety. SNP-based heritability was 5.9% (SE = 0.19%). Polygenic scores were significantly associated with anxiety symptom severity and disorder in European, African, and South Asian ancestry samples (r2=1.2%-3.4%). Significant genetic correlations were estimated with numerous mental and physical health traits, including case-control anxiety, neuroticism and depression (rg=0.71-0.86), irritable bowel syndrome (rg=0.57), coronary artery disease, endometriosis, and migraine (rg=0.20-0.27). Gene-based and pathway analyses implicated synaptic and axonal processes, with enriched expression in the brain. These findings highlight the additional value of a dimensional approach in anxiety genetics.