Predisposition locus for major depression at chromosome 12q22-12q23.2.
Major depression disorder is a common psychiatric disease with a major economic impact on society. In many cases, no effective treatment is available. The etiology of major depression is complex, but it is clear that the disease is, to a large extent, determined genetically, especially among individuals with a familial history of major depression, presumably through the involvement of multiple predisposition genes in addition to an environmental component. As a first step toward identification of chromosomal loci contributing to genetic predisposition to major depression, we have conducted a genomewide scan by using 628 microsatellite markers on 1,890 individuals from 110 Utah pedigrees with a strong family history of major depression. We identified significant linkage to major depression in males at marker D12S1300 (multipoint heterogeneity LOD score 4.6; P=.00003 after adjustment for multiple testing). With additional markers, the linkage evidence became highly significant, with the multipoint heterogeneity LOD score at marker D12S1706 increasing to 6.1 (P=.0000007 after adjustment for multiple testing). This study confirms the presence of one or more genes involved in psychiatric diseases on the q arm of chromosome 12 and provides strong evidence for the existence of a sex-specific predisposition gene to major depression at 12q22-q23.2.
Abkevich, V; Camp, NJ; Hensel, CH; Neff, CD; Russell, DL; Hughes, DC; Plenk, AM; Lowry, MR; Richards, RL; Carter, C; Frech, GC; Stone, S; Rowe, K; Chau, CA; Cortado, K; Hunt, A; Luce, K; O'Neil, G; Poarch, J; Potter, J; Poulsen, GH; Saxton, H; Bernat-Sestak, M; Thompson, V; Gutin, A; Skolnick, MH; Shattuck, D; Cannon-Albright, L
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