Largest Ever Genome-Wide Association Study Finds Genetic Risk Factors for Anxiety

Largest Ever Genome-Wide Association Study Finds Genetic Risk Factors for AnxietyLargest Ever Genome-Wide Association Study Finds Genetic Risk Factors for Anxiety

The largest study ever conducted on genetic risk factors for anxiety, a genome-wide association study (GWAS) of 200,000 participants recently published in the American Journal of Psychiatry, found significant associations between self-reported anxiety and specific single nucleotide polymorphisms (SNPs). Daniel Levey, PhD, from the department of psychiatry, Yale University School of Medicine, New Haven, Connecticut, and colleagues pulled data from one of the largest biobanks in the world, the Million Veteran Program. To assess anxiety and related disorders, researchers used the Generalized Anxiety Disorder 2-item scale (GAD-2), as well as self-reported physician diagnosis of an anxiety disorder. The study sample included individuals from European and African American backgrounds. In addition, the researchers carried out a conditional analysis for depression, given high rates of comorbidity between anxiety and depressive disorders. The investigators found 5 specific genome-wide significant loci for European Americans (near SATB1, ESR1, LINC01360/LRRIQ3, MAD1L1, and TCEA2/OPRL1) and 1 locus for African Americans (near TRPV6) based on GAD-2 scores. In multitrait-based conditional and joint analyses, SATB1, on chromosome 3, and ESR1, on chromosome 6, remained genome-wide significant. The researchers partially replicated the findings based on other previously published GWAS data. SNP heritability for anxiety ranged from 5.58% to 8.79% for GAD-2 and physician diagnosis of anxiety, respectively. Furthermore, depressive symptoms (P =1.95×10−53) and neuroticism (P =6.53×10−53) were genetically correlated with GAD-2 scores. In an analysis of polygenic risk scores, the researchers identified significant overlap between anxiety and major depressive disorder (variance explained, 0.24 ...
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