期刊
GENETIC EPIDEMIOLOGY
卷 31, 期 5, 页码 383-395出版社
WILEY
DOI: 10.1002/gepi.20219
关键词
complex trait; genotypes; haplotypes; principal components
资金
- NCI NIH HHS [CA52862] Funding Source: Medline
- NHLBI NIH HHS [HL061768] Funding Source: Medline
- NIEHS NIH HHS [ES011627, ES007048, ES009581] Funding Source: Medline
Current technology allows investigators to obtain genotypes at multiple single nucleotide polymorphism (SNPS) within a candidate locus. Many approaches have been developed for using such data in a test of association with disease, ranging from genotype-based to haplotype-based tests. We develop a new approach that involves two basic steps. In the first step, we use principal components (PCs) analysis to compute combinations of SNPs that capture the underlying correlation structure within the locus. The second step uses the PCs directly in a test of disease association. The PC approach captures linkage-disequilibrium information within a candidate region, but does not require the difficult computing implicit in a haplotype analysis. We demonstrate by simulation that the PC approach is typically as or more powerful than both genotype- and haplotype-based approaches. We also analyze association between respiratory symptoms in children and four SNPs in the Gluta thione-S-Transf erase P1 locus, based on data from the Children's Health Study. We observe stronger evidence of an association using the PC approach (p = 0.044) than using either a genotype-based (p = 0.13) or haplotypebased (p = 0.052) approach.
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