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Science. 2003 Oct 31;302(5646):822-6.

The genetics of adult-onset neuropsychiatric disease: complexities and conundra?

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  • 1Departments of Psychiatry and Medicine, Centre for Addiction and Mental Health, Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H9, Canada.


Genetic factors play a major role in the etiology of adult-onset neurodegenerative and neuropsychiatric disorders. Several highly penetrant genes have been cloned for rare, autosomal-dominant, early-onset forms of neurodegenerative diseases. These genes have provided important insights into the mechanisms of these diseases (often altering neuronal protein processing). However, the genes associated with inherited susceptibility to late-onset neurodegenerative diseases, schizophrenia, and bipolar disorder appear to have smaller effects and are likely to interact with each other (and with nongenetic factors) to modulate susceptibility and/or disease phenotype. Several strategies have recently been applied to address this complexity, leading to the identification of a number of candidate susceptibility loci/genes.

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