Predisposition Locus for Major Depression at Chromosome 12q22-12q23.2

Abstract

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.

Combined Linkage and Association Analyses of the 124-bp Allele of Marker D2S2944 with Anxiety, Depression, Neuroticism and Major Depression

“…Abkevich et al, 2003;Holmans et al, 2004;Zubenko et al, 2003b). Because of variation in populations, the criteria for selection of subjects and choice of phenotypes evidently can produce different results, one conclusion could be that this region is not involved in the development of MDD and related quantitative traits.…”

“…The effects were again female specific and occurred for recurrent MDD and less severe disorders, but not for recurrent early-onset MDD. The linkage studies of Holmans et al (2004) and Abkevich et al (2003) were genome wide. The results of Holmans While Zubenko et al (2002b, c) provided evidence for an association of the 124-bp allele of D2S2944 to recurrent/early-onset MDD, their linkage results on chromosome 2 (Zubenko et al, 2002a(Zubenko et al, , 2003b were obtained for disorders that were either less severe or more broadly defined than recurrent early-onset MDD.…”

A high-density SNP genome-wide linkage scan in a large autism extended pedigree

“…MCLINK has been used previously to identify candidate genomic regions for a number of complex diseases. [41][42][43][44] We performed a nonparametric linkage analysis, as inheritance models for autism in general and specifically for broad spectrum of autism are unknown. Ideally, we could have derived the inheritance model parameters from our sample and used them for analysis.…”

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

“…deCODE focuses on large pedigrees with distantly related affected members, who are expected to share shorter genome segments around a disease gene than the more closely related affected individuals in small pedigrees. Hence, deCODE conducted genome scans using denser marker sets than those used by most groups 68 , analyzing linkage in entire pedigrees with programs developed by its scientists 69 and considering several different combinations of phenotypic information in these analyses Although the scale of deCODE's extended pedigree studies is unusual, numerous research groups are using similar approaches, mainly in families from relatively closed populations [70][71][72][73][74][75] . These populations exist throughout the world and are characterized by low immigration, low emigration and distribution over relatively small areas, so that most subjects and their medical records are available to investigators.…”