2011年11月1日
Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders
Biological Psychiatry
- 巻
- 70
- 号
- 9
- 開始ページ
- 888
- 終了ページ
- 896
- 記述言語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.biopsych.2011.07.012
Background: Anxiety disorders are common psychiatric conditions that are highly comorbid with each other and related phenotypes such as depression, likely due to a shared genetic basis. Fear-related behaviors in mice have long been investigated as potential models of anxiety disorders, making integration of information from both murine and human genetic data a powerful strategy for identifying potential susceptibility genes for these conditions. Methods: We combined genome-wide association analysis of fear-related behaviors with strain distribution pattern analysis in heterogeneous stock mice to identify a preliminary list of 52 novel candidate genes. We ranked these according to three complementary sources of prior anxiety-related genetic data: 1) extant linkage and knockout studies in mice, 2) a meta-analysis of human linkage scans, and 3) a preliminary human genome-wide association study. We genotyped tagging single nucleotide polymorphisms covering the nine top-ranked regions in a two-stage association study of 1316 subjects from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders chosen for high or low genetic loading for anxiety-spectrum phenotypes (anxiety disorders, neuroticism, and major depression). Results: Multiple single nucleotide polymorphisms in the PPARGC1A gene demonstrated association in both stages that survived gene-wise correction for multiple testing. Conclusions: Integration of genetic data across human and murine studies suggests PPARGC1A as a potential susceptibility gene for anxiety-related disorders. © 2011 Society of Biological Psychiatry.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.biopsych.2011.07.012
- ISSN : 0006-3223
- eISSN : 1873-2402
- PubMed ID : 21871609
- SCOPUS ID : 80053932587