Human Molecular Genetics Advance Access originally published online on January 30, 2009
Human Molecular Genetics 2009 18(8):1504-1509; doi:10.1093/hmg/ddp051
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Depression Case Control (DeCC) Study fails to support involvement of the muscarinic acetylcholine receptor M2 (CHRM2) gene in recurrent major depressive disorder
1 MRC SGDP Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK 2 Department of Psychological Medicine, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK 3 Division of Neuroscience, Department of Psychiatry, University of Birmingham, The Barberry, 25 Vincent Drive, Edgbaston, Birmingham B15 2FG, UK 4 Centre for Psychiatry, Wolfson Institute of Preventive Medicine, Barts and The London, Charterhouse Square, London EC1M 6BQ, UK
* To whom correspondence should be addressed at: MRC SGDP Centre, Institute of Psychiatry, King's College London, Box PO82, De Crespigny Park, London, SE5 8AF, UK. Tel: +44 2078480856; Fax: +44 2078480866; Email: sarah.cohen{at}iop.kcl.ac.uk
Received November 3, 2008; Revised January 26, 2009; Accepted January 26, 2009
It has been suggested that alteration in the muscarinic-cholinergic system is involved in modulation of mood. Three studies have reported linkage on chromosome 7 with major depressive disorder (MDD) in or close to a region containing the muscarinic receptor CHRM2 gene. A haplotype of SNPs located in CHRM2 (rs1824024–rs2061174–rs324650) has been significantly associated with MDD in a previous study. We report the first study investigating this gene in a large, adequately powered, clinical depression case–control sample (n = 1420 cases, 1624 controls). Our data fail to support association with the CHRM2 polymorphisms previously implicated in the genetic aetiology of depression. It is possible our failure to replicate may be a consequence of differences in definition of the MDD phenotype and/or ethnic differences.