Alzheimer's disease: one disorder, too many genes?
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.
Bertram
Lars
L
Genetics and Aging Research Unit, Department of Neurology and Mass General Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Tanzi
Rudolph E
RE
D000544:Alzheimer Disease / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans