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DOI 10.1101/2025.07.10.25331321

Медицинская библиотека · medRxiv : the preprint server for health sciences · 2025

Genome-wide insights into generalised anxiety using a dimensional symptom severity approach.

Skelton Megan, Mitchell Brittany L, Assary Elham, Li Danyang, Morneau-Vaillancourt Genevieve, Murphy Alan E, Ter Kuile Abigail R, Wang Rujia, Adams Mark J, Byrne Enda M, Corfield Elizabeth C, Grimes Poppy Z, Hannigan Laurie J, Hu Jihua, Koiv Kadri, Kwong Alex Sf, Papiol Sergi, Pettersen Johanne H, Pistis Giorgio, Castelao Enrique, Strom Nora I, van der Most Peter J, Anxiety Disorders Working Group of the Psychiatric Genomics Consortium, GLAD+ authors, Lifelines Cohort Study, NIHR Bioresource, Protect-AD Consortium, Andreassen Ole A, Erhardt-Lehmann Angelika, Havdahl Alexandra, Skene Nathan, Verhulst Brad, Weber Heike, Armour Cherie, Ask Helga, Copeland William E, Dannlowski Udo, Deckert Jurgen, Domschke Katharina, Hickie Ian B, Lehto Kelli, Lonsdorf Tina B, Lueken Ulrike, Lupton Michelle K, Medland Sarah E, McIntosh Andrew M, Oldehinkel Albertine J, Preisig Martin, Reif Andreas, Snieder Harold, Walters James T R, Wray Naomi R, Hartman Catharina A, Martin Nicholas G, Hettema John M, Breen Gerome, Coleman Jonathan Ri, Eley Thalia C

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Аннотация

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.

Для цитирования: Skelton Megan, Mitchell Brittany L, Assary Elham, Li Danyang, Morneau-Vaillancourt Genevieve, Murphy Alan E, Ter Kuile Abigail R, Wang Rujia, Adams Mark J, Byrne Enda M, Corfield Elizabeth C, Grimes Poppy Z, Hannigan Laurie J, Hu Jihua, Koiv Kadri, Kwong Alex Sf, Papiol Sergi, Pettersen Johanne H, Pistis Giorgio, Castelao Enrique, Strom Nora I, van der Most Peter J, Anxiety Disorders Working Group of the Psychiatric Genomics Consortium, GLAD+ authors, Lifelines Cohort Study, NIHR Bioresource, Protect-AD Consortium, Andreassen Ole A, Erhardt-Lehmann Angelika, Havdahl Alexandra, Skene Nathan, Verhulst Brad, Weber Heike, Armour Cherie, Ask Helga, Copeland William E, Dannlowski Udo, Deckert Jurgen, Domschke Katharina, Hickie Ian B, Lehto Kelli, Lonsdorf Tina B, Lueken Ulrike, Lupton Michelle K, Medland Sarah E, McIntosh Andrew M, Oldehinkel Albertine J, Preisig Martin, Reif Andreas, Snieder Harold, Walters James T R, Wray Naomi R, Hartman Catharina A, Martin Nicholas G, Hettema John M, Breen Gerome, Coleman Jonathan Ri, Eley Thalia C. Genome-wide insights into generalised anxiety using a dimensional symptom severity approach.. medRxiv : the preprint server for health sciences. 2025. DOI: 10.1101/2025.07.10.25331321.
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