Zhang Heping, Leckman James F, Pauls David L, Tsai Chin-Pei, Kidd Kenneth K, Campos M Rosario
Department of Epidemiology and Public Health, Yale Child Study Center, Yale University School of Medicine, 60 College Street, New Haven, CT 06520-8034, USA.
Am J Hum Genet. 2002 Apr;70(4):896-904. doi: 10.1086/339520. Epub 2002 Feb 11.
A genome scan of the hoarding phenotype (a component of obsessive-compulsive disorder) was conducted on 77 sib pairs collected by the Tourette Syndrome Association International Consortium for Genetics (TSAICG). All sib pairs were concordant for a diagnosis of Gilles de la Tourette syndrome (GTS). However, the analyses reported here were conducted for hoarding as both a dichotomous trait and a quantitative trait. Not all sib pairs in the sample were concordant for hoarding. Standard linkage analyses were performed using GENEHUNTER and Haseman-Elston methods. In addition, novel analyses with a recursive-partitioning technique were employed. Significant allele sharing was observed for both the dichotomous and the quantitative hoarding phenotypes for markers at 4q34-35 (P=.0007), by use of GENEHUNTER, and at 5q35.2-35.3 (P=.000002) and 17q25 (P=.00002), by use of the revisited Haseman-Elston method. The 4q site is in proximity to D4S1625, which was identified by the TSAICG as a region linked to the GTS phenotype. The recursive-partitioning technique examined multiple markers simultaneously. Results suggest joint effects of specific loci on 5q and 4q, with an overall P value of.000003. Although P values were not adjusted for multiple comparison, nearly all were much smaller than the customary significance level of.0001 for genomewide scans.
国际抽动秽语综合征遗传学协会联盟(TSAICG)收集了77对同胞对,对囤积行为表型(强迫症的一个组成部分)进行了全基因组扫描。所有同胞对均被诊断为抽动秽语综合征(GTS)。然而,此处报告的分析是针对囤积行为作为一种二分性状和一种数量性状进行的。样本中的并非所有同胞对在囤积行为上都是一致的。使用GENEHUNTER和哈斯曼 - 埃尔斯顿方法进行了标准连锁分析。此外,还采用了递归划分技术进行新的分析。通过使用GENEHUNTER方法发现,在4q34 - 35处的标记对于二分和数量囤积行为表型均观察到显著的等位基因共享(P = 0.0007),通过使用改进的哈斯曼 - 埃尔斯顿方法发现,在5q35.2 - 35.3(P = 0.000002)和17q25(P = 0.00002)处也有显著的等位基因共享。4q位点靠近D4S1625,TSAICG已将其确定为与GTS表型相关的区域。递归划分技术同时检查了多个标记。结果表明5q和4q上的特定基因座存在联合效应,总体P值为0.000003。尽管未对多重比较进行P值调整,但几乎所有P值都远小于全基因组扫描通常的显著性水平0.0001。