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Human Molecular Genetics Advance Access originally published online on October 3, 2005
Human Molecular Genetics 2005 14(22):3337-3345; doi:10.1093/hmg/ddi363
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Whole genome linkage scan of recurrent depressive disorder from the depression network study

Peter McGuffin1,*, Jo Knight1, Gerome Breen1, Shyama Brewster2, Peter R. Boyd2, Nick Craddock3,11, Mike Gill4, Ania Korszun5, Wolfgang Maier6, Lefkos Middleton2, Ole Mors7, Michael J. Owen3, Julia Perry2, Martin Preisig8, Theodore Reich9, John Rice9, Marcella Rietschel10, Lisa Jones11, Pak Sham1 and Anne E. Farmer1

1Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London SE5 8AF, UK, 2GlaxoSmithKline, Research and Development, Greenford UB6 0HE, UK, 3Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff CF10 3XQ, UK, 4Department of Psychiatry, Trinity Centre for Health Sciences, Dublin 8, Ireland, 5Barts and The London, Queen Mary's School of Medicine and Dentistry, London E1 4NS, UK, 6Department of Psychiatry, University of Bonn, 53127 Bonn, Germany, 7Department of Psychiatry, University of Aarhus, DK-8000 Aarhus, Denmark, 8Department of Adult Psychiatry, University Hospital of Lausanne, 1008 Prilly-Lausanne, Switzerland, 9Department of Psychiatry, Washington University, St Louis, MO 63130, USA, 10Central Institute of Mental Health, 68159 Mannheim, Germany and 11Department of Psychiatry, University of Birmingham, Birmingham, UK

* To whom correspondence should be addressed at: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, PO Box 80, De Crespigny Park, London SE5 8AF, UK. Tel: +44 2078480871; Fax: +44 2078480866; Email: p.mcguffin{at}iop.kcl.ac.uk

Received June 2, 2005; Revised September 7, 2005; Accepted September 23, 2005

Genome-wide linkage analysis was carried out in a sample of 497 sib pairs concordant for recurrent major depressive disorder (MDD). There was suggestive evidence for linkage on chromosome 1p36 where the LOD score for female–female pairs exceeded 3 (but reduced to 2.73 when corrected for multiple testing). The region includes a gene, MTHFR, that in previous studies has been associated with depressive symptoms. Two other regions, on chromosomes 12q23.3–q24.11 and 13q31.1–q31.3, showed evidence for linkage with a nominal P<0.01. The 12q peak overlaps with a region previously implicated by linkage studies of unipolar and bipolar disorders and contains a gene, DAO, that has been associated with both bipolar disorder and schizophrenia. The 13q peak lies within a region previously linked strongly to panic disorder. A fourth modest peak with an LOD of greater than 1 on chromosome 15q lies within a region that showed genome-wide significant evidence of a recurrent depression locus in a previous sib-pair study. Both the 12q and the 15q findings remained significant at genome-wide level when the data from the present study and the previous reports were combined.


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