Beecham Gary W, Naj Adam C, Gilbert John R, Haines Jonathan L, Buxbaum Joseph D, Pericak-Vance Margaret A
John P. Hussman Institute for Human Genomics, Dr John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA.
Psychiatr Genet. 2010 Dec;20(6):321-4. doi: 10.1097/YPG.0b013e32833b635d.
A recent genome-wide association study and follow-up shows significant association with the protocadherin 11 X-linked (PCDH11X) gene. Carrasquillo et al. (2009) show statistical association with four PCDH11X polymorphisms (rs5984894, rs2573905, rs5941047, rs4568761) in five of seven cohorts. The combined analysis of 2356 cases and 2384 controls showed the strongest association with a P value of 2.2×10 with an allele-specific odds ratio of 1.30 (95% confidence interval, 1.18-1.43) at the rs5984894 polymorphism. We tested for association at these four single nucleotide polymorphisms in two independent datasets and then performed a joint analysis. Although we had adequate power to detect effect sizes with the reported odds ratios, we did not detect association between late-onset Alzheimer disease and the PCDH11X polymorphisms in our dataset of 889 cases and 850 controls, indicating that the PCDH11X association, if not a false positive, is not as strong or generalized as hypothesized earlier.
最近一项全基因组关联研究及后续研究表明，与X连锁原钙黏蛋白11（PCDH11X）基因存在显著关联。卡拉斯基洛等人（2009年）在七个队列中的五个队列里，发现了PCDH11X的四个多态性位点（rs5984894、rs2573905、rs5941047、rs4568761）存在统计学关联。对2356例病例和2384例对照的联合分析显示，rs5984894多态性位点的关联最强，P值为2.2×10，等位基因特异性比值比为1.30（95%置信区间为1.18 - 1.43）。我们在两个独立数据集中对这四个单核苷酸多态性位点进行了关联测试，然后进行了联合分析。尽管我们有足够的检验效能以报告的比值比来检测效应大小，但在我们包含889例病例和850例对照的数据集中，未检测到晚发型阿尔茨海默病与PCDH11X多态性位点之间存在关联，这表明PCDH11X的关联（若不是假阳性）并不像之前假设的那么强或普遍。
