※ [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. 敬 請 公 佈 歡 迎 參加 --

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