[Mapping genes of major recurrent depression in genetic isolates]

We conducted a genome-wide linkage scan in two extended pedigrees ascertained from two Dagestan genetic isolates (N(o)6007 and 6008) with high aggregation of early onset major depressive disorders (MDD). The first pedigree included in total 22 cases of MDD (15 available) and 11 suicides; the second pedigree contained 29 MDD cases (23 available) and 12 suicides. Five linked regions in our study are consistent with previous findings in association and/or linkage studies with MDD: 11p15, 12q23-24, 13q11-32, 18q22 and 22q11-13. We found two novel for early onset MDD genomic regions with significant linkages in N(o)6007 with Lods = 3.1-3.4 at 2p13.2-p11.2 (and some weak signal in the same region for N(o)6008) and at 14q31.12-q32.13. We also obtained suggestive level linkages at 9q33.3-q34.2 (N(o)6008), 13q31.1-q31.2 (N(o)6007), 11p15 (N(o)6008), 17q25.3 (N(o)6007) and 19q13.31-q13.33 (N(o)6008). Six linked regions (1p36.1-p35.2, 2p13.2-p11.2,13q31, 17q25.3, 18q22 and 22q12.3) were consistent across the two isolates' pedigrees while all other linkage regions (5q14.1-q14.3, 9q33.3-q34.2, 13q31.1-q32.1, 14q31.12-q32.13, 20p13) demonstrated population-specific genetic heterogeneity of MDD. Our results suggest that genetic mapping of complex diseases, including MDD, across genetically homogeneous isolates can enrich the harvest of linkage signals and expedite the search for susceptibility genes.