Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders.
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 integr...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1797067838209392640 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hettema, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T22:02:06Z |
| format | Journal article |
| id | oxford-uuid:4ef29f7c-7694-466d-9319-8961ea1f8c8a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:02:06Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:4ef29f7c-7694-466d-9319-8961ea1f8c8a2022-03-26T16:04:10ZPrioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4ef29f7c-7694-466d-9319-8961ea1f8c8aEnglishSymplectic Elements at Oxford2011Hettema, JWebb, BGuo, AZhao, ZMaher, BChen, XAn, SSun, CAggen, SKendler, KKuo, POtowa, TFlint, Jvan den Oord, EBACKGROUND: 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. |
| spellingShingle | 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 Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders. |
| title | Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders. |
| title_full | Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders. |
| title_fullStr | Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders. |
| title_full_unstemmed | Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders. |
| title_short | Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders. |
| title_sort | prioritization and association analysis of murine derived candidate genes in anxiety spectrum disorders |
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