Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
 

Learn about the flu shot, COVID-19 vaccine, and our masking policy »

Stanford Health Care

A novel age-informed approach for genetic association analysis in Alzheimer's disease. Alzheimer's research & therapy Le Guen, Y., Belloy, M. E., Napolioni, V., Eger, S. J., Kennedy, G., Tao, R., He, Z., Greicius, M. D., Alzheimers Disease Neuroimaging Initiative 2021; 13 (1): 72

Abstract

BACKGROUND: Many Alzheimer's disease (AD) genetic association studies disregard age or incorrectly account for it, hampering variant discovery.METHODS: Using simulated data, we compared the statistical power of several models: logistic regression on AD diagnosis adjusted and not adjusted for age; linear regression on a score integrating case-control status and age; and multivariate Cox regression on age-at-onset. We applied these models to real exome-wide data of 11,127 sequenced individuals (54% cases) and replicated suggestive associations in 21,631 genotype-imputed individuals (51% cases).RESULTS: Modeling variable AD risk across age results in 5-10% statistical power gain compared to logistic regression without age adjustment, while incorrect age adjustment leads to critical power loss. Applying our novel AD-age score and/or Cox regression, we discovered and replicated novel variants associated with AD on KIF21B, USH2A, RAB10, RIN3, and TAOK2 genes.CONCLUSION: Our AD-age score provides a simple means for statistical power gain and is recommended for future AD studies.

View details for DOI 10.1186/s13195-021-00808-5

View details for PubMedID 33794991