Department of Mathematical Sciences, Michigan Technological University, Houghton, MI, USA.
Eur J Hum Genet. 2011 Jul;19(7):801-6. doi: 10.1038/ejhg.2011.35. Epub 2011 Mar 9.
For haplotype analysis of the X chromosome, haplotype-sharing (HS) statistics with sliding windows are defined for males and females separately, which are then combined to a single HS test for the X chromosome. When independent replication samples are not available, the training-testing sets approach is used to validate this procedure and a permutation method is used to obtain its P-value. We applied this method to the X chromosome (with 1804 SNPs) for age-related macular degeneration (AMD). We found a window of five SNPs over a 272 kb region associated with AMD after Bonferroni correction. An examination of the odds ratio and the population attributable risks revealed a disease-preventive haplotype, ATGAC, on these five SNPs. For elderly females without this haplotype, the likelihood of AMD is increased by a factor of 4.75 with a 95% confidence interval (1.43, 15.82). The frequency of ATGAC in HapMap CEU is 0.276. These five SNPs are covered by the gene DIAPH2, which is known to cause premature ovarian failure (POF) in females. Our results indicated that DIAPH2 may be a polygenic pleiotropy for POF and AMD.
对于 X 染色体的单体型分析，分别为男性和女性定义单体型共享（HS）统计数据，然后将其组合为 X 染色体的单个 HS 检验。当没有独立的复制样本时，使用训练-测试集方法来验证此过程，并使用置换方法获得其 P 值。我们将这种方法应用于与年龄相关的黄斑变性（AMD）相关的 X 染色体（包含 1804 个 SNP）。经过 Bonferroni 校正后，我们在 272 kb 区域中发现了一个与 AMD 相关的五个 SNP 的窗口。对这些五个 SNP 上的比值比和人群归因风险进行检查，揭示了一种预防疾病的单体型 ATGAC。对于没有这种单体型的老年女性，AMD 的可能性增加了 4.75 倍，置信区间为 1.43，15.82。在 HapMap CEU 中，ATGAC 的频率为 0.276。这五个 SNP 由 DIAPH2 基因覆盖，该基因已知会导致女性卵巢早衰（POF）。我们的结果表明，DIAPH2 可能是 POF 和 AMD 的多基因复合性。
