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Science 31 October 2003: Vol. 302. no. 5646, pp. 822 - 826 DOI: 10.1126/science.1092132
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Review
The Genetics of Adult-Onset Neuropsychiatric Disease: Complexities and Conundra?
James L. Kennedy,1
Lindsay A. Farrer,2
Nancy C. Andreasen,3
Richard Mayeux,4
Peter St George-Hyslop1*
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.
1 Departments of Psychiatry and Medicine, Centre for Addiction and Mental Health, Centre for Research in Neurodegenerative Diseases, University of Toronto; and Department of Medicine (Division of Neurology), The University Health Network, Toronto, Ontario M5S 3H9, Canada.
2 Departments of Medicine, Neurology, and Genetics & Genomics, Boston University School of Medicine; and Departments of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
3 Department of Psychiatry, University of Iowa; and Departments of Psychiatry and Neurology, University of New Mexico, The MIND Institute, Albuquerque, NM 87106, USA.
4 Gertrude H. Sergievsky Center, Taub Institute of Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
* To whom correspondence should be addressed. E-mail: p.hyslop{at}utoronto.ca
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