Reaching the Limits of Genome-wide Significance in Alzheimer Disease
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- Nancy L. Pedersen, PhD
- Author Affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Since this article does not have an abstract, we have provided the first 150 words of the full text.
- KEYWORDS:
- AGING
- ALZHEIMER DISEASE
- ENVIRONMENTAL EXPOSURE
- GENETIC PREDISPOSITION TO DISEASE
- GENETIC RESEARCH
- GENOME, HUMAN
- GENOME-WIDE ASSOCIATION STUDY
- RISK FACTORS
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.
Seshadri et al have provided an exemplary demonstration of the process by which information from multiple sources, often including multiple consortia and replication samples, potentiates finding reliable, significant results. However, the value of continued attempts to find genetic effects of diminishing …
