Dopamine transporter gene (DAT1) VNTR polymorphism in major psychiatric disorders: family-based association study in the Bulgarian population

Objective: A 40-bp variable number tandem repeat in the 3′-UTR of dopamine transporter gene (DAT1) has been examined for association with major psychiatric disorders in several case–control studies. No significant results have been found. We used a new collection of parent–offspring trios to test for association with schizophrenia (SZ), bipolar 1 disorder (BPI) and schizoaffective (SA) disorder. Method: We genotyped trios from Bulgarian origin where the proband had SZ (178 trios), BPI (77 trios) and SA (29 trios). Alleles ranging from 5 to 11 repeats were observed. The results were analysed with the extended TDT (ETDT). Results: No preferential transmission of alleles was observed for any diagnostic group. The presence of allele DAT*10 was associated with the severity and frequency of auditory hallucinations, however, this result is not significant if corrected for multiple testing. Conclusion: Our results are in agreement with previous reports of a lack of association between this polymorphism and major psychiatric disorders

A transmission disequilibrium and linkage analysis of D22S278 marker alleles in 574 families: further support for a susceptibility locus for schizophrenia at 22q12

Previously, a combined analysis by the Chromosome 22 Collaborative Linkage Group (1996; Am. J. Med Genet. 67, 40-45) used an affected sib-pair analysis of a single marker (D22S278) in 574 families multiply affected by schizophrenia and found some evidence for linkage (λ = 9.35, 1 df, p = 0.001), suggesting the presence of a disease locus nearby on chromosome 22q12. In order to further investigate the importance of this result, we have performed the transmission disequilibrium test (TDT) and additional parametric and non-parametric linkage analysis of the same data. The most positive result obtained was an admixture lod score of 0.9 under the assumption of locus heterogeneity and dominant transmission. The result of the TDT analysis was significant at p = 0.015 (allele-wise; λ = 22, 10 df) and p = 0.00016 (genotype-wise; λ = 66.2, 30 df, empirical p value = 0.0009). Overall, these results further strengthen the notion that there is a susceptibility locus for schizophrenia close to D22S278