Sir

Your News Feature ‘The brains of the family’ (Nature 454, 154–157; 2008) summarizes the problems in the hunt for genetic variants associated with psychiatric disorders. But it contains ambiguities that, coupled with strong opinions from leading geneticists and neuroscientists, leave an unnecessarily dire impression of the field.

The News Feature gives DISC1 ('disrupted-in-schizophrenia 1') as a prototypical example of a gene bearing variants that fail to manifest consistently in the clinic — something that often plagues psychiatric genetics. As you imply, these failures are at odds with the clear association of certain genetic variants and rare mutations with an increased risk of a particular disease, such as Alzheimer's.

However, selective pressures may prevent mutations associated with strong deleterious effects from spreading into more common variants. The failure of large-scale, genome-wide and candidate-gene association studies to reliably detect common risk variants in DISC1 does not diminish the significance of the rare DISC1 structural mutation found in the Scottish family mentioned in the News Feature, nor the possibility of other rare DISC1 mutations affecting disease risk. Keeping an open mind is important, given increasing evidence that rare structural mutations play a major role in the aetiology of psychiatric disorders (see Nature doi:10.1038/news.2008.994; 2008).

Efforts are under way to combine the best approaches from genetics and neuroscience. Genome-wide association studies for intermediate phenotypes are being linked with psychiatric disorders, circumventing the bias inherent in candidate-gene investigations and the questionable validity of current diagnostic labels (R. M. Bilder Biol. Psychiat. 63, 439–440; 2008).

I hope that today's students and young researchers will not inherit the ideological baggage of their fields, but rather will be armed with the tools needed to tackle specific problems, regardless of departmental or disciplinary borders.

See also: Mental health: maybe human troubles don't fit into set categories Mental health: don't overlook environment and its risk factors