background Depression has a strong genetic component, but the candidate gene studies conducted to date have not shown consistent associations.
aim To find genes involved in depression.
methods We conducted a genome-wide parametric and non-parametric linkage analysis in a large-scale family-based study. Further we investigated the most promising chromosomal regions found in the genome-wide linkage analysis with an association analysis in a larger sample of the same family-based study and in a populationbased study. The linkage analyses included data of 115 individuals from the family-based study with depression, who were identified based on the Hospital Anxiety Depression Scale (hads-d), Center for Epidemiologic Studies Depression Rating Scale (ces-d) or use of anti-depressive medication. The regions of interest were studied detail with high density genotyping in 734 individuals in the family-based study and 2,373 individuals in the population-based study.
results Our study demonstrated evidence for significant linkage of depression to chromosome 2p16.1-15 (lod = 5.13; parametric analysis) and suggestive evidence for linkage in nonparametric analysis to chromosome 5p15.33 (lod = 2.14), 11q25 (lod = 2.27) and 19p13.3 (lod = 2.66). The subsequent association analysis in the familybased study showed region-wide significant association in intron 1 of the opcml gene on chromosome 11q25 (empirical p-value = 0.04). The association analysis in the population-based study did not show any region-wide significant association, yet showed suggestive association in intron 1 of the aplp2 gene on chromosome 11q25.
conclusion Our linkage and association studies suggest a locus for depression on chromosome 2p16.1-15 and 11q25 .The linkage to chromosome 11q25 may be in part explained by the opcml or the aplp2 gene. Further there is evidence for a role of the gng7 gene (chromosome 19 p13.3).