Dysfunction of the central serotonergic system has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The genetic contribution to the development of OCD is particularly high in early-onset OCD. The aim of this study was to investigate the effect of polymorphic variants in the gene of the novel brain-specific tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme of serotonin (5-HT) synthesis in the brain, in OCD with disease onset in childhood and adolescence. We analysed two common single nucleotide polymorphisms (SNPs) of TPH2 in the putative transcriptional control region and in intron 2 of the TPH2 gene in a unique family-based sample of OCD patients with onset of the disease in childhood and adolescence comprising 71 complete, independent trios. The transmission disequilibrium test was used to determine transmission of alleles and haplotypes from parents to offspring. In this first study of TPH2 in OCD, analysis of the SNPs, rs4570625 and rs4565946, revealed a significant preferential transmission of haplotype G-C to children and adolescents with OCD. Moreover, a trend towards preferential transmission of the C allele of SNP rs4565946 to the patients was found. The genotype relative-risk estimate for homozygous C allele carriers of SNP rs4565946 was 2.58 (95% CI 0.98-6.82). In conclusion, the results link TPH2 variations to the pathogenesis of early-onset OCD and further support the aetiological relevance of 5-HT signalling in OCD.

The distribution of the blood group systems ABO, Rhesus, MNSs and P was studied in all or some of 1,007 Singapore Chinese. ABO gene frequencies were found to be consistent with previous studies and did not vary significantly between dialects. An individual of phenotype A₂B was detected although the population showed no other evidence for the A₂ gene. The possible significance of this observation in terms of weak H alleles in the population is discussed. The frequencies of the MNSs genes are consistent with previous studies. Two subjects appeared to lack the N^A component of the N antigen. The frequency of the R₁ gene of the Rhesus system was lower than has been detected previously and may relate to dialect differences. No examples of the C^w antigen were detected. The P blood group distribution appears to be subject to regional variation. It is concluded that classification of Chinese into dialect groups is a useful way of assessing genetic heterogeneity.

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