Psychiatry

Correlating Variants and Variation

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Science  24 Jun 2005:
Vol. 308, Issue 5730, pp. 1843
DOI: 10.1126/science.308.5730.1843d

Genetic factors are widely believed to play a role in the etiology of schizophrenia, a debilitating psychiatric disorder that affects about 1% of the population. However, identifications of specific contributory genes and of critical sequence variants in those genes have not been unambiguous, because the disorder likely arises through the interactions of multiple genes, each exerting a weak effect.

To distinguish critical sequence variants in the DISC1 (disrupted-in-schizophrenia) candidate gene from background noise, Callicott et al. studied whether any of the putative risk-conferring variants correlated with biological features of schizophrenia. Intriguingly, they found that in healthy people, one particular disease- associated variant of DISC1 appears to adversely influence the anatomical structure and cognitive functioning of the hippocampal formation, which has long been a focal point of pathological studies of schizophrenia. These results thus support the hypothesis that variation in the DISC1 gene is a contributing factor in the development of schizophrenia and likely acts, at least in part, through its effects on the hippocampus. — PAK

Proc. Natl. Acad. Sci. U.S.A. 102, 8627 (2005).

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