Essays on Science and SocietyGenome-Sequencing Anniversary

The Meaning of the Human Genome Project for Neuropsychiatric Disorders

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Science  25 Feb 2011:
Vol. 331, Issue 6020, pp. 1026
DOI: 10.1126/science.1203544

The past 3 years have witnessed a series of replicable, credible, and increasingly useful genetic discoveries in autism, schizophrenia, and bipolar disorder. I cannot emphasize enough the significance of this progress. Neuropsychiatric disorders are outsized contributors to global disease burden, yet treatment development has reached a near stand-still. The problem is that the brain, with its myriad cell types and complex circuitry, represents such a difficult scientific frontier. Because genes play powerful roles in neuropsychiatric disorders, identification of causal variation could provide invaluable clues to their pathogenesis. Sadly, the genetic architecture of neuropsychiatric disorders is fiendishly complex, but unlike other areas of medicine wrestling with genetic complexity, psychiatry lacks objective phenotypic markers.

When I became director of the National Institute of Mental Health (NIMH), NIH, in 1996, I did not foresee quite how complex the genetics would prove, but did recognize that the contemporary technologies were overmatched. (I ruefully joked that I had the only institute with no low-hanging Mendelian fruit to pluck.) With expert advice, I decided that the only rational approach was to amass large collections of patient DNAs with extensive phenotype information. Some investigators resisted sharing of samples, but for most, that day has long passed. I am pleased that these NIMH collections have proven useful, albeit as only a small fraction of the needed sample sizes.

It was not, of course, the first human sequence per se that turned the tide for neuropsychiatric disorders. As for much of medicine, the associated technologies and analytic approaches (above all, the availability of ever cheaper and more accurate DNA sequencing) are proving decisive. These advances have given investigators, clinicians, and patients hope that genetics will finally yield tools that neurobiologists have dreamt of to study the brain in health and in illness.


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