Human Molecular Genetics Advance Access originally published online on February 5, 2004
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Human Molecular Genetics, 2004, Vol. 13, Review Issue 1 R135-R141
DOI: 10.1093/hmg/ddh077
Alzheimer's disease: one disorder, too many genes?
Genetics and Aging Research Unit, Department of Neurology and MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
The research of Alzheimer's disease (AD) genetics has been extremely prolific over the past decade, and currently more than 10 genes are reported to show either positive or negative evidence for disease association per month. Here, we review all 90 studies from 2003 reporting a total of 127 association findings between candidate genes and AD. While most positive results were largely contradictory, we identified three loci—on chromosomes 6p21, 10q24, 11q23—that yielded positive results in three or more independent studies, in addition to the well-established AD association with the gene encoding apolipoprotein E (APOE). Based on these data, we suggest that it may be prudent for investigators to pay closer attention to issues such as power, replicability and haplotype structure prior to initial publication. This should serve to greatly decrease the likelihood of false positive and false negative findings reported in future years.
* To whom correspondence should be addressed at: Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA. Tel: +1 6177266845; Fax: +1 6177241823; Email: tanzi{at}helix.mgh.harvard.edu
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