Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders.

Hettema, J; Webb, B; Guo, A; Zhao, Z; Maher, B; Chen, X; An, S; Sun, C; Aggen, S; Kendler, K; Kuo, P; Otowa, T; Flint, J; van den Oord, E

Journal article

Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders.

Abstract:: 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.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Cite

Cite this record

APA Style

Hettema, J., Webb, B., Guo, A., Zhao, Z., Maher, B., Chen, X., An, S., Sun, C., Aggen, S., Kendler, K., Kuo, P., Otowa, T., Flint, J., & van den Oord, E. (2011). Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders. Biological Psychiatry, 70(9), 888–896.

MLA Style

Hettema, J., et al. “Prioritization and Association Analysis of Murine-Derived Candidate Genes in Anxiety-Spectrum Disorders.” Biological Psychiatry, vol. 70, no. 9, 2011, pp. 888–96.

Chicago Style

Hettema, J, B Webb, A Guo, Z Zhao, B Maher, X Chen, S An, et al. 2011. “Prioritization and Association Analysis of Murine-Derived Candidate Genes in Anxiety-Spectrum Disorders.” Biological Psychiatry 70 (9): 888–96.
Share
Print