Effects of cutoff thresholds for minor allele frequencies on HapMap resolution: A real dataset-based evaluation of the Chinese Han and Tibetan populations  

作　　者：XIONG ShiYi HAO YuanTao RAO ShaoQi HUANG WeiJun HU Bin Labu Pubuzhuoma Gesangzhuogab WANG YiMing 

机构地区：[1]Department of Medical Genetics, Zhongshan Medical College, Sun Yat-sen University, Guangzhou 510089, China [2]Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510089, China [3]Department of Gynecology and Obstetrics, the 2nd Hospital of the Tibetan Autonomous Region, Lhasa 850002, China

出　　处：《Chinese Science Bulletin》2009年第12期2069-2075,共7页

基　　金：Supported by the Key Construction Program of the National"985"Project of China(Phase Ⅱ);Natural Science Foundation of Guangdong Province(Grant No.031673);Guang-zhou Municipal Science and Technology Foundation(Grant Nos.2002Z3-C7191,2004Z3-C7501)

摘　　要：Genomic variation is the genetic basis of phenotypic diversity among individuals, including variation in disease susceptibility and drug response. The greatest promise of the International HapMap is to provide roadmaps for identifying genetic variants predisposing to complex diseases. Single nucleotide polymorphism (SNP) is the fundamental element of the HapMap. Allele frequency of SNPs is one of the major factors affecting the resulting HapMap, being the factor upon which linkage disequilibrium (LD) is calculated, haplotypes are constructed, and tagging SNPs (tagSNPs) are selected. The cutoff thresholds for the frequency of minor alleles used in the making of the map therefore have profound effects on the resolution of that map. To date most researchers have adopted their own cutoff thresholds, and there has been little real dataset-based evaluation of the effects of different cutoff thresholds on HapMap resolution. In an attempt to assess the implications of different cutoff values, we analyzed our own data for the centromeric genes on Chromosome 15 in Chinese Han and Tibetan populations, with respect to minor allele frequency cutoff values of ≥0.01 (0.01 group), ≥0.05 (0.05 group), and ≥0.10 (0.10 group), and constructed HapMaps from each of the datasets. The resolution, study power and cost-effectiveness for each of the maps were compared. Our results show that the 0.01 threshold pro- vides the greatest power (P = 0.019 in Han and P = 0.029 in Tibetan for 0.01 vs. 0.05 threshold) and detects most population-specific haploypes (P = 0.012 for 0.01 vs. 0.05 threshold). However, in the regions studied, the 0.05 cutoff threshold did not significantly increase power above the 0.10 threshold (P = 0.191 in Han; 1.000 in Tibetans), and did not improve resolution over the 0.10 value for population-specific haplotypes (P = 0.592) neither. Furthermore the 0.05 and 0.10 values produced the same figures for tagging efficiency, LD block number, LD length, study power and cost-savings in the Tibetan population. These rGenomic variation is the genetic basis of phenotypic diversity among individuals, including variation in disease susceptibility and drug response. The greatest promise of the International HapMap is to provide roadmaps for identifying genetic variants predisposing to complex diseases. Single nucleotide polymorphism （SNP） is the fundamental element of the HapMap. Allele frequency of SNPs is one of the major factors affecting the resulting HapMap, being the factor upon which linkage disequilibrium （LD） is calculated, haplotypes are constructed, and tagging SNPs （tagSNPs） are selected. The cutoff thresholds for the frequency of minor alleles used in the making of the map therefore have profound effects on the resolution of that map. To date most researchers have adopted their own cutoff thresh- olds, and there has been little real dataset-based evaluation of the effects of different cutoff thresholds on HapMap resolution. In an attempt to assess the implications of different cutoff values, we analyzed our own data for the centromeric genes on Chromosome 15 in Chinese Han and Tibetan populations, with respect to minor allele frequency cutoff values of 〉0.01 （0.01 group）, 〉0.05 （0.05 group）, and 〉0.10 （0.10 group）, and constructed HapMaps from each of the datasets. The resolution, study power and cost-effectiveness for each of the maps were compared. Our results show that the 0.01 threshold provides the greatest power （P= 0.019 in Han and P= 0.029 in Tibetan for 0.01 vs. 0.05 threshold） and de- tects most population-specific haploypes （P= 0.012 for 0.01 vs. 0.05 threshold）. However, in the regions studied, the 0.05 cutoff threshold did not significantly increase power above the 0.10 threshold （P = 0.191 in Han; 1.000 in Tibetans）, and did not improve resolution over the 0.10 value for population- specific haplotypes （P= 0.592） neither. Furthermore the 0.05 and 0.10 values produced the same figures for tagging efficiency, LD block number, LD length, study power and cost-sav

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分 类 号：Q987[生物学—遗传学] TV143[生物学—人类学]