Common psychiatric diseases and human genetic variation

A better understanding of human genetic variation is important in assessing disease epidemiology and phenotypic variation, and may be critical in evaluating genetic aspects of common genetic diseases, such as schizophrenia, bipolar disease and Parkinson's. These diseases are particularly difficult to investigate as there are few peripheral markers, and although a genetic aetiology has long been suspected, robust findings have been hard to establish.

Variations in alleles at 13 tri-nucleotide gene loci expressed in the brain and implicated in several neurodegenerative diseases, as well as certain other loci, were examined in the Indian population for comparison with other major ethnic groups.

In the Indian population, the distribution of alleles at the Machado-Joseph disease locus was similar to the Western European pattern of distribution. Analysis of haplotypes at the locus for Huntington's disease suggested multiple origins, and possible effects of population admixture because of the recent history of the country. At other alleles of neuropsychiatric interest (dopamine receptor, serotonin receptor, serotonin transporter, alcohol dehydrogenase), allele frequencies in the Indian population differed from other populations. Interspecies comparison suggests a gradual expansion in repeat size, with the exception of the CLOCK gene, which displays a contraction of CAG repeat numbers. World-wide differences in disease phenotypes need to be explored, and an appreciation of their genetic basis may provide a window of opportunity for improving our knowledge of the underlying genetic mechanisms.