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Featured Clinical Reviews

May 12, 2010

Reaching the Limits of Genome-wide Significance in Alzheimer Disease: Back to the Environment

Author Affiliations

Author Affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

JAMA. 2010;303(18):1864-1865. doi:10.1001/jama.2010.609

In this issue of JAMA, Seshadri et al1 present a 3-stage approach to genome-wide association studies (GWAS) involving more than 35 000 individuals to identify novel genes for late-onset Alzheimer disease (AD). As has been the case for an increasing number of common, complex diseases, results for a few new loci reached genome-wide significance and other previously reported associations were replicated. The authors also addressed the contributions of these genes to disease risk prediction and conclude, perhaps not surprisingly, that the loci did not significantly improve AD risk prediction. Nevertheless, Seshadri et al point out that the results implicate biological pathways that may provide important targets for interventions.

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