title: A genome-wide linkage study in families with major depression and co-morbid unexplained swelling.
abstract: Major depressive disorder (MDD) is a common heritable condition. The diversity of the phenotype coupled with aetiological and genetic heterogeneity present formidable obstacles in the search for causative genetic loci. Studies of large families with many affected individuals, and the selection of well-defined clinical subgroups of depression, are two ways to reduce this complexity. Unexplained swelling symptoms (USS) are common in women and many patients give a strong personal and family history of depression. Co-morbid depression and swelling symptoms define a useful sub-phenotype for investigating genetic factors in depression. We have completed a genome-wide linkage analysis using 371 microsatellite markers in four families where MDD is co-morbid with USS. Of 47 affected individuals, 28 had both MDD and unexplained swelling, 11 had symptoms of swelling alone, and 8 had MDD alone. Parametric marker-specific analysis identified one suggestive locus, D8S260 (LOD = 2.02) and non-parametric multipoint variance component analysis identified a region on 7p (LOD = 2.10). A 47 cM suggestive linkage region on chromosome 14q (identified by both parametric and non-parametric methods) was identified and investigated further with fine-mapping markers but the evidence for linkage to this region decreased with increased marker information content.
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Anderson
authors.forename: Alan
authors.initials: A
authors.lastname: Maclean
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Dunnigan
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Pelosi
authors.forename: Valerie
authors.initials: V
authors.lastname: Murray
authors.forename: Irene
authors.initials: I
authors.lastname: McKee
authors.forename: George
authors.initials: G
authors.lastname: McDonald
authors.forename: David W
authors.initials: DW
authors.lastname: Burt
authors.forename: David R
authors.initials: DR
authors.lastname: Morrice
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Muir
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
authors.forename: Douglas H R
authors.initials: DH
authors.lastname: Blackwood
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003865:Major Depressive Disorder / Q000235:genetics*; D004487:Edema / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype