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Human Molecular Genetics Advance Access published online on October 3, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi363
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© The Author 2005. Published by Oxford University Press. All rights reserved
Received June 2, 2005
Revised September 7, 2005
Accepted September 23, 2005

Article

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

Peter McGuffin 1*, Jo Knight 2, Gerome Breen 2, Shyama Brewster 3, Peter R Boyd 3, Nick Craddock 4, Mike Gill 5, Ania Korszun 6, Wolfgang Maier 7, Lefkos Middleton 3, Ole Mors 8, Michael J Owen 4, Julia Perry 3, Martin Preisig 9, Theodore Reich 10, John Rice 10, Marcella Rietschel 11, Lisa Jones 12, Pak Sham 2, and Anne E Farmer 2

1 Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Box PO80, De Crespigny Park, King's College London, London SE5 8AF, UK
2 Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London SE5 8AF, UK
3 GlaxoSmithKline, Research and Development, Greenford UB6 0HE, UK
4 Dept of Psychological Medicine, School of Medicine, Cardiff University, Cardiff CF10 3XQ, UK
5 Department of Psychiatry, Trinity Centre for Health Sciences, Dublin 8, Eire
6 Barts and The London, Queen Mary's School of Medicine and Dentistry, London E1 4NS, UK
7 Department of Psychiatry, University of Bonn, 53127 Bonn, Germany
8 Department of Psychiatry, University of Aarhus, DK-8000 Aarhus, Denmark
9 Department of Adult Psychiatry, University Hospital of Lausanne, 1008 Prilly-Lausanne, Switzerland
10 Dept of Psychiatry, Washington University, St Louis MO-63130, USA
11 Central Institute of Mental Health, 68159 Mannheim, Germany
12 Department of Psychiatry, University of Birmingham

* To whom correspondence should be addressed.
Peter McGuffin, E-mail: p.mcguffin{at}iop.KCL.ac.uk


  Abstract

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 was 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 chromosome 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 disorder 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 a LOD of > 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 data from the present study and the previous reports were combined.


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