Year: 2012
Type: dissertation
Study design: Observational Study
Abstract: Anxiety disorders, such as panic disorder (PD), obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, and phobias are common psychiatric disorders, characterized by exaggerated, prolonged and debilitating levels of anxiety. They are complex diseases with onset influenced by both environmental and genetic factors, but so far little progress has been made in identifying solid susceptibility genes. The aim of this study was to shed light on the genetic basis of human anxiety disorders by genetic analyses of putative susceptibility genes. Altogether, 333 single nucleotide polymorphism markers from 30 genes were tested for genetic association to anxiety disorders in a sample (N = 974) derived from the Finnish population-based Health 2000 cohort. Three other samples from Spain (N = 503), Sweden (N = 2020) and USA (N = 1128) were used for replication attempts or meta-analyses. The studied genes were 1) selected based on a mouse model of anxiety-like behavior; 2) an asthma-linked receptor (neuropeptide S receptor 1; NPSR1) and its neuropeptide ligand (neuropeptide S; NPS); and 3) selected based on previous findings in anxiety disorders or anxiety-related personality traits. We also evaluated whether any of the studied genes modulate probability for anxiety disorders in interaction with childhood adverse life events, which are strong environmental risk factors for anxiety disorders. First, with a cross-species approach, we discovered that six of the murine candidate genes associated with specific human anxiety disorders. The implicated genes link novel biological pathways to anxiety susceptibility. Second, NPSR1 and NPS associated with PD in adults, and symptoms of anxiety/depression in children. Our findings suggest that NPS-NPSR1 signaling modulates predisposition not only to asthma, but also to anxiety. Third, of the putative susceptibility genes examined based on previous studies, the strongest associations were for glutamate decarboxylase 1 (GAD1) with phobias. Our results, together with previous findings in the gene, support the role of GAD1 as a risk factor for anxiety- and mood disorders, and neuroticism. Fourth, the neuropeptide Y (NPY) gene modulated the effects of the number of experienced childhood adversities on anxiety susceptibility. NPY may therefore influence individual variation in stress resilience. In conclusion, we identified altogether ten potential susceptibility genes for anxiety disorders. They should be further evaluated in independent study samples, and studied functionally to understand how they may regulate behavior. Such future studies will be essential for evaluating their therapeutic potential in treatment of anxiety disorders. Our findings also support the notion that understanding of the interplay between environmental risk factors and genetic variants is important for understanding predisposition to psychiatric disorders.
Source: Työväentutkimus Vuosikirja
Author: Jonas Donner
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1523245996