应用连锁不平衡图谱的关联研究分析方法

目的提出一种对高通量单核苷酸多态位点(single nucleotide polymorphism,SNP)关联研究的数据分析方法。方法在160名上海地区中国人中进行754个SNP的基因型检测,分别构建病例组和对照组的连锁不平衡(linkage disequilibrium,LD)图谱,通过比较两组间染色体区域LD图谱随物理距离的变化趋势寻找与疾病相关的位点,并与传统LD分析以及SNP单点、单倍型分析进行比较。结果LD图谱的分析能判断出两组间LD存在差异的染色体区域,并且该区域SNP等位基因频率和单倍型频率在两组间分布存在统计学差异或差异趋势。结论可应用该方法对高通量SNP的关联研究进行数据分析。

An analysis method to apply linkage disequilibrium maps to association study

Objective To apply linkage disequilibrium(LD) maps to associations studies with high throughput single nucleotide polymorphisms(SNPs).Methods Seven hundred and fifty-four SNPs were genotyped in 160 Shanghai Chinese.LD maps were constructed in cases and controls separately.By comparing the decline of LD unit with distance between the two groups,disease susceptible loci were estimated.This method was compared with traditional analyses including LD analysis,single SNP and haplotype analyses.Results The analysis of LD maps could detect the chromosome regions with different LD patterns between the cases and controls.The alleles and/or haplotypes frequencies of SNPs within the regions had significantly different distributions or trends of significantly different distributions.Conclusion This method may be applied to analyze the data from association studies with high throughput SNPs genotype information.