An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders
Background Human anxiety disorders are complex diseases with largely unknown etiology. We have taken a cross-species approach to identify genes that regulate anxiety-like behavior with inbred mouse strains that differ in their innate anxiety levels as a model. We previously identified 17 genes wi...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2012
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| Online Access: | http://hdl.handle.net/1721.1/70928 |
| _version_ | 1826202141012787200 |
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| author | Donner, Jonas Pirkola, Sami Silander, Kaisa Kananen, Laura Terwilliger, Joseph D. Lonnqvist, Jouko Hovatta, Iiris Peltonen, Leena |
| author2 | Broad Institute of MIT and Harvard |
| author_facet | Broad Institute of MIT and Harvard Donner, Jonas Pirkola, Sami Silander, Kaisa Kananen, Laura Terwilliger, Joseph D. Lonnqvist, Jouko Hovatta, Iiris Peltonen, Leena |
| author_sort | Donner, Jonas |
| collection | MIT |
| description | Background
Human anxiety disorders are complex diseases with largely unknown etiology. We have taken a cross-species approach to identify genes that regulate anxiety-like behavior with inbred mouse strains that differ in their innate anxiety levels as a model. We previously identified 17 genes with expression levels that correlate with anxiety behavior across the studied strains. In the present study, we tested their 13 known human homologues as candidate genes for human anxiety disorders with a genetic association study.
Methods
We describe an anxiety disorder study sample derived from a Finnish population-based cohort and consisting of 321 patients and 653 carefully matched control subjects, all interviewed to obtain DSM-IV diagnoses. We genotyped altogether 208 single nucleotide polymorphisms (SNPs) (all non-synonymous SNPs, SNPs that alter potential microRNA binding sites, and gap-filling SNPs selected on the basis of HapMap information) from the investigated anxiety candidate genes.
Results
Specific alleles and haplotypes of six of the examined genes revealed some evidence for association (p ≤ .01). The most significant evidence for association with different anxiety disorder subtypes were: p = .0009 with ALAD (δ-aminolevulinate dehydratase) in social phobia, p = .009 with DYNLL2 (dynein light chain 2) in generalized anxiety disorder, and p = .004 with PSAP (prosaposin) in panic disorder.
Conclusions
Our findings suggest that variants in these genes might predispose to specific human anxiety disorders. These results illustrate the potential utility of cross-species approaches in identification of candidate genes for psychiatric disorders. |
| first_indexed | 2024-09-23T12:03:09Z |
| format | Article |
| id | mit-1721.1/70928 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:03:09Z |
| publishDate | 2012 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/709282022-10-01T07:47:28Z An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders Donner, Jonas Pirkola, Sami Silander, Kaisa Kananen, Laura Terwilliger, Joseph D. Lonnqvist, Jouko Hovatta, Iiris Peltonen, Leena Broad Institute of MIT and Harvard Peltonen, Leena Peltonen, Leena Background Human anxiety disorders are complex diseases with largely unknown etiology. We have taken a cross-species approach to identify genes that regulate anxiety-like behavior with inbred mouse strains that differ in their innate anxiety levels as a model. We previously identified 17 genes with expression levels that correlate with anxiety behavior across the studied strains. In the present study, we tested their 13 known human homologues as candidate genes for human anxiety disorders with a genetic association study. Methods We describe an anxiety disorder study sample derived from a Finnish population-based cohort and consisting of 321 patients and 653 carefully matched control subjects, all interviewed to obtain DSM-IV diagnoses. We genotyped altogether 208 single nucleotide polymorphisms (SNPs) (all non-synonymous SNPs, SNPs that alter potential microRNA binding sites, and gap-filling SNPs selected on the basis of HapMap information) from the investigated anxiety candidate genes. Results Specific alleles and haplotypes of six of the examined genes revealed some evidence for association (p ≤ .01). The most significant evidence for association with different anxiety disorder subtypes were: p = .0009 with ALAD (δ-aminolevulinate dehydratase) in social phobia, p = .009 with DYNLL2 (dynein light chain 2) in generalized anxiety disorder, and p = .004 with PSAP (prosaposin) in panic disorder. Conclusions Our findings suggest that variants in these genes might predispose to specific human anxiety disorders. These results illustrate the potential utility of cross-species approaches in identification of candidate genes for psychiatric disorders. National Institute of Mental Health (U.S.) 2012-05-24T18:04:39Z 2012-05-24T18:04:39Z 2008-07 2008-05 Article http://purl.org/eprint/type/JournalArticle 0006-3223 http://hdl.handle.net/1721.1/70928 Donner, Jonas et al. “An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders.” Biological Psychiatry 64.8 (2008): 672–680. Web. 24 May 2012. © 2008 Society of Biological Psychiatry en_US http://dx.doi.org/10.1016/j.biopsych.2008.06.002 Biological Psychiatry Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Donner, Jonas Pirkola, Sami Silander, Kaisa Kananen, Laura Terwilliger, Joseph D. Lonnqvist, Jouko Hovatta, Iiris Peltonen, Leena An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders |
| title | An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders |
| title_full | An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders |
| title_fullStr | An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders |
| title_full_unstemmed | An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders |
| title_short | An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders |
| title_sort | association analysis of murine anxiety genes in humans implicates novel candidate genes for anxiety disorders |
| url | http://hdl.handle.net/1721.1/70928 |
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