Meta‐analysis of association between obsessive‐compulsive disorder and the 3′ region of neuronal glutamate transporter gene SLC1A1 |
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Authors: | SE Stewart C Mayerfeld PD Arnold JR Crane C O'Dushlaine JA Fagerness D Yu JM Scharf E Chan F Kassam PR Moya JR Wendland R Delorme MA Richter JL Kennedy J Veenstra‐VanderWeele J Samuels BD Greenberg JT McCracken JA Knowles AJ Fyer SL Rauch MA Riddle MA Grados OJ Bienvenu B Cullen Y Wang YY Shugart J Piacentini S Rasmussen G Nestadt DL Murphy MA Jenike EH Cook DL Pauls GL Hanna CA Mathews |
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Institution: | 1. McLean Hospital, Belmont, Massachusetts;2. Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts;3. Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts;4. Harvard Medical School, Boston, Massachusetts;5. University of British Columbia, Vancouver, British Columbia, Canada;6. British Columbia Mental Health and Addictions Research Institute Vancouver, British Columbia, Canada;7. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada;8. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada;9. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, Massachusetts;10. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts;11. Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts;12. Intramural Research Program, NIMH, Bethesda, Maryland;13. CNS Clinical Biomarker Group, Pharma Research and Early Development, F. Hoffmann‐La Roche Ltd., Basel, Switzerland;14. Department of Child and Adolescent Psychiatry, AP‐HP, Robert Debré Hospital, INSERM U955, Paris, France;15. Institut Mondor de Recherche Biomédicale, Psychiatric Genetics, Créteil, France;16. Foundation Fondamental, French National Science Foundation, Paris, France;17. Department of Psychiatry, Clinic for OCD and Related Disorders, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada;18. Psychiatric Neurogenetics Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada;19. Departments of Psychiatry, Pediatrics, and Pharmacology, Vanderbilt Kennedy Center for Research on Human Development and Vanderbilt Brain Institute, Nashville, Tennessee;20. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland;21. Department of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Providence, Rhode Island;22. Department of Psychiatry and Biobehavioral Sciences, School of Medicine, University of California, Los Angeles, California;23. Department of Psychiatry and The Behavioral Sciences, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California;24. Department of Psychiatry, College of Physicians and Surgeons at Columbia University and the New York State Psychiatric Institute, New York, New York;25. Partners Psychiatry and Mental Health, Belmont, Massachusetts;26. Department of Psychiatry, Institute for Juvenile Research, University of Illinois at Chicago, Chicago, Illinois;27. Department of Psychiatry, University of Michigan, Ann Arbor, Michigan;28. Department of Psychiatry, University of California, San Francisco, California |
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Abstract: | The neuronal glutamate transporter gene SLC1A1 is a candidate gene for obsessive‐compulsive disorder (OCD) based on linkage studies and convergent evidence implicating glutamate in OCD etiology. The 3′ end of SLC1A1 is the only genomic region with consistently demonstrated OCD association, especially when analyzing male‐only probands. However, specific allele associations have not been consistently replicated, and recent OCD genome‐wide association and meta‐analysis studies have not incorporated all previously associated SLC1A1 SNPs. To clarify the nature of association between SLC1A1 and OCD, pooled analysis was performed on all available relevant raw study data, comprising a final sample of 815 trios, 306 cases and 634 controls. This revealed weak association between OCD and one of nine tested SLC1A1 polymorphisms (rs301443; uncorrected P = 0.046; non‐significant corrected P). Secondary analyses of male‐affecteds only (N = 358 trios and 133 cases) demonstrated modest association between OCD and a different SNP (rs12682807; uncorrected P = 0.012; non‐significant corrected P). Findings of this meta‐analysis are consistent with the trend of previous candidate gene studies in psychiatry and do not clarify the putative role of SLC1A1 in OCD pathophysiology. Nonetheless, it may be important to further examine the potential associations demonstrated in this amalgamated sample, especially since the SNPs with modest associations were not included in the more highly powered recent GWAS or in a past meta‐analysis including five SLC1A1 polymorphisms. This study underscores the need for much larger sample sizes in future genetic association studies and suggests that next‐generation sequencing may be beneficial in examining the potential role of rare variants in OCD. © 2013 Wiley Periodicals, Inc. |
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Keywords: | obsessive‐compulsive disorder OCD candidate gene meta‐analysis SLC1A1 glutamate |
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