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

Peter McGuffin, Jo Knight, Gerome Breen, Shyama Brewster, Peter R. Boyd, Nick Craddock, Mike Gill, Ania Korszun, Wolfgang Maier, Lefkos Middleton, Ole Mors, Michael J. Owen, Julia Perry, Martin Preisig, Theodore Reich, John Rice, Marcella Rietschel, Lisa Jones, Pak Sham, Anne E. Farmer

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135 Scopus citations


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.

Original languageEnglish
Pages (from-to)3337-3345
Number of pages9
JournalHuman molecular genetics
Issue number22
StatePublished - Nov 15 2005


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