Genetic heterogeneity of schizophrenia.

The cumulative evidence from over a century of research overwhelmingly implicates genes in the etiology of Schizophrenia. Twin studies consistently find higher rates of schizophrenia among cotwins of monozygotic compared with dizygotic twins and adoption studies show that familial transmission is mediated by genetic, not adoptive relationships. Nevertheless, the hunt for schizophrenia genes with molecular genetic technologies has been disappointing. Although the available literature suggests that cytogenetic abnormalities cause some cases of schizophrenia, these abnormalities must account for only a small fraction of all schizophrenia. Attempts to scan the entire genome with DNA markers spaced at regular intervals have failed to produce unequivocal linkage findings. Notably, several groups have reported findings suggestive of linkage to chromosome 22 and other work provides weak evidence of a gene on the sex chromosomes. The search for schizophrenia genes has been complicated by its unknown mode of transmission, the possibility of phenocopies and genetic heterogeneity.