[轉錄]0618演講公告＠交大統研所
※ [本文轉錄自 NCTU-STAT96G 看板]
作者: cyz ( ) 看板: NCTU-STAT96G
標題: 0618演講公告＠交大統研所
時間: Tue Jun 10 20:12:35 2008
國立交通大學、清華大學
統計學研究所
專題演講
題 目：
From Glutathione S-Transferase Omega-1 (GSTO1) and -2 (GSTO2) for
age-at-onset of Alzheimer disease to a Novel Family-based Association Method
主講人：李怡如教授(Duke University Medical Center)
時 間：97年6月18日(星期三)下午13:00-13:50
(中午12:00-13:00茶會於交大統計所428室舉行，敬備餐盒)
地 點：交大綜合一館427室
Abstract
We previously reported genetic linkage of loci controlling age-at-onset in
Alzheimer disease (AD) to a 15 cM region on chromosome 10q. Given the large
number of genes in this initial starting region, we applied our process of “
genomic convergence” to prioritize and reduce the number of candidate genes
for further analysis. As our second convergence factor we performed gene
expression studies on hippocampus obtained from AD patients and controls.
Analysis revealed that four of the genes (Stearoyl-CoA desaturase ;
NADH-ubiquinone oxidoreductase 1 beta complex 8 ; protease, serine 11; and
glutathione S-transferase, omega-1 (GSTO1)) were significantly different in
their expression between AD and controls, and mapped to the 10q age-at-onset
linkage region, the first convergence factor. Using 2814 samples from our AD
dataset (1773 AD patients), allelic association studies for age-at-onset
effects in AD revealed no association for three of the candidates, but a
significant association was found for GSTO1 (P=0.007) and a second
transcribed member of the GST omega class, GSTO2 (P=0.005), located next to
GSTO1. However, the family-based association methods used in this study
focus on quantitative traits only. Since age-at-onset data are censored among
unaffected individuals, we subsequently developed a Genetic Association Tests
based On Ranks (GATOR) program to analyzed familial quantitative data with
and without censoring. The GATOR method was found to have increasing power
in comparison to existing methods (e.g. the QTDT program) when censor rate
increases. In addition, GATOR performed better than the logrank and Wilcoxon
methods implemented in FBAT program under certain scenario. We applied the
GATOR program to GSTO1 and GSTO2, and both genes remain highly significant.
As GSTO1 may be involved in the post-translational modification of the
inflammatory cytokine Interleukin-1β, these two candidate genes may play an
important role in regulating age-at-onset of AD.
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