Genetic Variants Associated With Anxiety and Stress-Related Disorders

Abstract

IMPORTANCE Anxiety and stress-related disorders are among the most common mental disorders. Although family and twin studies indicate that both genetic and environmental factors play an important role underlying their etiology, the genetic underpinnings of anxiety and stress-related disorders are poorly understood. OBJECTIVES To estimate the single-nucleotide polymorphism-based heritability of anxiety and stress-related disorders; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to evaluate the association of psychiatric comorbidities with genetic findings. DESIGN, SETTING, PARTICIPANTS This genome-wide association study included individuals with various anxiety and stress-related diagnoses and controls derived from the population-based Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) study. Lifetime diagnoses of anxiety and stress-related disorders were obtained through the national Danish registers. Genes of interest were further evaluated in mice exposed to chronic social defeat. The study was conducted between June 2016 and November 2018. MAIN OUTCOMES AND MEASURES Diagnoses of a relatively broad diagnostic spectrum of anxiety and stress-related disorders. RESULTS The study sample included 12 655 individuals with various anxiety and stress-related diagnoses and 19 225 controls. Overall, 17 740 study participants (55.6%) were women.

Genome‐wide association study of shared liability to anxiety disorders in Army STARRS

“…We note that two other anxiety disorder GWAS have been published since these analyses were performed. The first, conducted in 12,655 individuals with registry‐derived ICD‐10 anxiety and/or stress‐related disorders and 19,225 unscreened controls from the Danish Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) cohort, reported one genome‐wide significant association with variants in the PDE4B gene (Meier et al, ). The second, conducted in 25,453 cases with self‐reported any lifetime anxiety disorder and 58,113 controls from the UK Biobank cohort, identified five novel genome‐wide significant loci including variants in the gene for NTRK2 , a receptor for brain‐derived neurotropic factor (Purves et al, ).…”

Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish

“…Stress evokes multiple behavioral and physiological responses 1 , 2 , including neuroendocrine and immune deficits 3 – 7 , that may trigger common affective illnesses, such as anxiety, depression and post-traumatic stress disorder (PTSD) 8 – 11 . Widespread, debilitating and often treatment-resistant, these neuropsychiatric disorders represent an urgent unmet biomedical problem 12 – 14 , complicated by their multiple overlapping genetic and environmental determinants, and poor understanding of their mechanisms and risk factors 15 , 16 . Animal models, especially employing rodents, are widely used to study stress biology and pathogenesis 17 – 19 .…”

The genetic and environmental hierarchical structure of anxiety and depression in the UK Biobank

“…Studies using this approach are beginning to show that common genetic variants (single‐nucleotide polymorphism; SNP) account for individual differences in depression and anxiety. Findings indicate that SNP‐based heritability of anxiety and depression varies between 0.10 and 0.30 (Howard et al, 2019; Meier et al, 2019; Otowa et al, 2016; Purves et al, 2019; Wray et al, 2018). SNP heritability is one way to show the cumulative contribution of a subset of SNPs to a trait's total heritability (Bulik‐Sullivan, Loh et al, 2015).…”