Generalised Anxiety Disorder--A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression.
Generalised Anxiety Disorder--A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression.
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DOI：
10.1371/journal.pone.0134865
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Spector TD
中科院分区：
文献类型：
--
作者：
Davies MN;Verdi S;Burri A;Trzaskowski M;Lee M;Hettema JM;Jansen R;Boomsma DI;Spector TD
广泛性焦虑症（GAD）是一种常见的焦虑相关诊断，影响约5%的成年人口。广泛性焦虑症的一个特征是高度的焦虑敏感性（AS），这是一种描述对唤醒相关感觉的恐惧的人格特质。在这里，我们提出了一个全基因组的关联研究AS使用队列的730 MZ和DZ女性双胞胎。GWAS显示出与RBFOX 1基因内的变体的显著关联。同一队列的遗传力分析也证实了一个显着的遗传成分，h2为0.42。此外，使用RNA-seq数据研究了队列的一个子集（25例AS不一致的MZ双胞胎）的差异表达证据。观察到ITM 2B基因在不一致的MZ亚群中的两个外显子的显著差异表达，这一发现在一个独立的队列中重复。虽然以前的研究表明，焦虑与各种精神和神经退行性疾病有很高的共病性，我们的分析表明，一个新的病因学特定于AS。
Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was studied for evidence of differential expression using RNA-seq data. Significant differential expression of two exons with the ITM2B gene within the discordant MZ subset was observed, a finding that was replicated in an independent cohort. While previous research has shown that anxiety has a high comorbidity with a variety of psychiatric and neurodegenerative disorders, our analysis suggests a novel etiology specific to AS.