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An efficient weighted tag SNP-set analytical method in genome-wide association studies.

Yan B, Wang S, Jia H, Liu X, Wang X - BMC Genet. (2015)

Bottom Line: The intensive simulation results show that the power of weighted tag SNP-set-based test is much higher than that of weighted original SNP-set-based test and that of un-weighted tag SNP-set-based test.The simulation results indicate the method of selecting tag SNP-set impacts the power greatly and the power of our proposed method is the highest.From the analysis of simulated replicated data sets, we came to a conclusion that weighted tag SNP-set-based test is a powerful SNP-set test in GWAS.

View Article: PubMed Central - PubMed

Affiliation: College of Mathematics and Systems Science, Shandong University of Science and Technology, Qingdao, Shandong, 266590, China. 890612@163.com.

ABSTRACT

Background: Single-nucleotide polymorphism (SNP)-set analysis in Genome-wide association studies (GWAS) has emerged as a research hotspot for identifying genetic variants associated with disease susceptibility. But most existing methods of SNP-set analysis are affected by the quality of SNP-set, and poor quality of SNP-set can lead to low power in GWAS.

Results: In this research, we propose an efficient weighted tag-SNP-set analytical method to detect the disease associations. In our method, we first design a fast algorithm to select a subset of SNPs (called tag SNP-set) from a given original SNP-set based on the linkage disequilibrium (LD) between SNPs, then assign a proper weight to each of the selected tag SNP respectively and test the joint effect of these weighted tag SNPs. The intensive simulation results show that the power of weighted tag SNP-set-based test is much higher than that of weighted original SNP-set-based test and that of un-weighted tag SNP-set-based test. We also compare the powers of the weighted tag SNP-set-based test based on four types of tag SNP-sets. The simulation results indicate the method of selecting tag SNP-set impacts the power greatly and the power of our proposed method is the highest.

Conclusions: From the analysis of simulated replicated data sets, we came to a conclusion that weighted tag SNP-set-based test is a powerful SNP-set test in GWAS. We also designed a faster algorithm of selecting tag SNPs which include most of information of original SNP-set, and a better weighted function which can describe the status of each tag SNP in GWAS.

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Related in: MedlinePlus

Power comparisons of different SNP-sets for SKAT. This shows the power comparisons of SKAT, SKAT-tag, Weighted SKAT and Weighted SKAT-tag at the significant level of 0.05.
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Fig2: Power comparisons of different SNP-sets for SKAT. This shows the power comparisons of SKAT, SKAT-tag, Weighted SKAT and Weighted SKAT-tag at the significant level of 0.05.

Mentions: To further verify the performance of our method, we apply it on SKAT. Table 5 shows that the type I error of our method can be controlled. Figure 2 plots the power comparison of SKAT, SKAT-tag, Weighted SKAT and Weighted SKAT-tag in scenario 2 and Table 6 lists their powers in scenario 3–9. The results also demonstrate our proposed weighted tag SNP-set analytical method is effective in disease association. To estimate the influence of the selection of the tag SNP-set on the test power, we compare the powers of the weighted SKAT-tag based on four types of tag SNP-sets: the original SNP-set, all tag SNPs selected by our proposed algorithm of selecting, all remaining SNPs and a randomly selected subset. Figure 3 indicates that the power of the weighted SKAT-tag based on the tag SNP-set selected by our proposed algorithm is the largest.Table 5


An efficient weighted tag SNP-set analytical method in genome-wide association studies.

Yan B, Wang S, Jia H, Liu X, Wang X - BMC Genet. (2015)

Power comparisons of different SNP-sets for SKAT. This shows the power comparisons of SKAT, SKAT-tag, Weighted SKAT and Weighted SKAT-tag at the significant level of 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4373116&req=5

Fig2: Power comparisons of different SNP-sets for SKAT. This shows the power comparisons of SKAT, SKAT-tag, Weighted SKAT and Weighted SKAT-tag at the significant level of 0.05.
Mentions: To further verify the performance of our method, we apply it on SKAT. Table 5 shows that the type I error of our method can be controlled. Figure 2 plots the power comparison of SKAT, SKAT-tag, Weighted SKAT and Weighted SKAT-tag in scenario 2 and Table 6 lists their powers in scenario 3–9. The results also demonstrate our proposed weighted tag SNP-set analytical method is effective in disease association. To estimate the influence of the selection of the tag SNP-set on the test power, we compare the powers of the weighted SKAT-tag based on four types of tag SNP-sets: the original SNP-set, all tag SNPs selected by our proposed algorithm of selecting, all remaining SNPs and a randomly selected subset. Figure 3 indicates that the power of the weighted SKAT-tag based on the tag SNP-set selected by our proposed algorithm is the largest.Table 5

Bottom Line: The intensive simulation results show that the power of weighted tag SNP-set-based test is much higher than that of weighted original SNP-set-based test and that of un-weighted tag SNP-set-based test.The simulation results indicate the method of selecting tag SNP-set impacts the power greatly and the power of our proposed method is the highest.From the analysis of simulated replicated data sets, we came to a conclusion that weighted tag SNP-set-based test is a powerful SNP-set test in GWAS.

View Article: PubMed Central - PubMed

Affiliation: College of Mathematics and Systems Science, Shandong University of Science and Technology, Qingdao, Shandong, 266590, China. 890612@163.com.

ABSTRACT

Background: Single-nucleotide polymorphism (SNP)-set analysis in Genome-wide association studies (GWAS) has emerged as a research hotspot for identifying genetic variants associated with disease susceptibility. But most existing methods of SNP-set analysis are affected by the quality of SNP-set, and poor quality of SNP-set can lead to low power in GWAS.

Results: In this research, we propose an efficient weighted tag-SNP-set analytical method to detect the disease associations. In our method, we first design a fast algorithm to select a subset of SNPs (called tag SNP-set) from a given original SNP-set based on the linkage disequilibrium (LD) between SNPs, then assign a proper weight to each of the selected tag SNP respectively and test the joint effect of these weighted tag SNPs. The intensive simulation results show that the power of weighted tag SNP-set-based test is much higher than that of weighted original SNP-set-based test and that of un-weighted tag SNP-set-based test. We also compare the powers of the weighted tag SNP-set-based test based on four types of tag SNP-sets. The simulation results indicate the method of selecting tag SNP-set impacts the power greatly and the power of our proposed method is the highest.

Conclusions: From the analysis of simulated replicated data sets, we came to a conclusion that weighted tag SNP-set-based test is a powerful SNP-set test in GWAS. We also designed a faster algorithm of selecting tag SNPs which include most of information of original SNP-set, and a better weighted function which can describe the status of each tag SNP in GWAS.

Show MeSH
Related in: MedlinePlus