Department of Statistics Seminar
North Carolina State University

presents

Dr. Yi-Ju Li

Duke University

"Modulation of Age at Onset and Risk in Alzheimer Disease"

ABSTRACT

Alzheimer disease (AD) is the leading cause of dementia in the elderly. Controversy has surrounded whether the effect of genes on late-onset AD is primarily modulating onset or risk. Most studies have modeled the risk of AD as a simple qualitative dichotomous trait. However, examining age-at-onset (AAO) as a quantitative trait can provide novel information and more directly model modulation of onset. We recently performed a genome scan of 455 families for AD risk. We have now analyzed AAO as a truncated quantitative trait using the variance-components approach (SOLAR; Almasy and Blangero, 1998) to identify quantitative trait loci (QTL). 1121/2821 individuals were affected (mean AAO: 72.8(6.8 years), 746 were unaffected at the time of exam (mean AOE: 70.2(13.0years) and the rest were unknown. Two polygenic models were considered: one included sex and affection status as covariates, the other included sex, affection status, and apolipoprotein E (APOE) genotypes as covariates. Interestingly, these analyses identified two novel regions and only one region that overlapped with any proposed region harboring risk genes for AD. The three identified regions were found on chromosomes 4 (LOD=2.29 and 1.84 for each model, respectively); 8 (LOD=2.09 and 2.09); and 10 (LOD=2.39 and 2.58). The known effect of APOE on AAO was detected only when the polymorphism itself was tested (LOD=3.28). In general, including APOE as a covariate slightly increased the LOD scores. These data suggest at least one gene (APOE) modulates both risk and onset, while others modulate only onset or risk.

Friday, November, 16, 2001

3:35 - 4:35 pm

206 Cox Hall

Refreshments will be served on the second floor of Dabney Hall (left of Room 222) at 3:00 pm.