Zheng Gang, Joo Jungnam, Zhang Chun, Geller Nancy L
Office of Biostatistics Research, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892-7938, USA.
Genet Epidemiol. 2007 Dec;31(8):834-43. doi: 10.1002/gepi.20244.
Test statistics for association between markers on autosomal chromosomes and a disease have been extensively studied. No research has been reported on performance of such test statistics for association on the X chromosome. With 100,000 or more single-nucleotide polymorphisms (SNPs) available for genome-wide association studies, thousands of them come from the X chromosome. The X chromosome contains rich information about population history and linkage disequilibrium. To identify X-linked marker susceptibility to a disease, it is important to study properties of various statistics that can be used to test for association on the X chromosome. In this article, we compare performance of several approaches for testing association on the X chromosome, and examine how departure from Hardy-Weinberg equilibrium would affect type I error and power of these association tests using X-linked SNPs. The results are applied to the X chromosome of Klein et al. [2005], a genome-wide association study with 100K SNPs for age-related macular degeneration. We found that a SNP (rs10521496) covered by DIAPH2, known to cause premature ovarian failure (POF) in females, is associated with age-related macular degeneration.
常染色体上的标记与疾病之间关联的检验统计量已得到广泛研究。但关于此类检验统计量在X染色体上关联的性能，尚无研究报道。在全基因组关联研究中，有100,000个或更多的单核苷酸多态性（SNP），其中数千个来自X染色体。X染色体包含有关群体历史和连锁不平衡的丰富信息。为了确定X连锁标记对疾病的易感性，研究可用于检验X染色体上关联的各种统计量的性质很重要。在本文中，我们比较了几种用于检验X染色体上关联的方法的性能，并研究偏离哈迪-温伯格平衡如何影响使用X连锁SNP的这些关联检验的I型错误和检验效能。结果应用于Klein等人[2005年]的X染色体，这是一项针对年龄相关性黄斑变性的100K SNP全基因组关联研究。我们发现，DIAPH2覆盖的一个SNP（rs10521496）与年龄相关性黄斑变性相关，已知该SNP会导致女性过早卵巢功能衰竭（POF）。
