Abstract
Single-nucleotide polymorphisms (SNPs) determined based on SNP arrays from the international HapMap consortium (HapMap) and the genetic variants detected in the 1000 genomes project (1KGP) can serve as two references for genomewide association studies (GWAS). We conducted comparative analyses to provide a means for assessing concerns regarding SNP array-based GWAS findings as well as for realistically bounding expectations for next generation sequencing (NGS)-based GWAS. We calculated and compared base composition, transitions to transversions ratio, minor allele frequency and heterozygous rate for SNPs from HapMap and 1KGP for the 622 common individuals. We analysed the genotype discordance between HapMap and 1KGP to assess consistency in the SNPs from the two references. In 1KGP, 90.58% of 36,817,799 SNPs detected were not measured in HapMap. More SNPs with minor allele frequencies less than 0.01 were found in 1KGP than HapMap. The two references have low discordance (generally smaller than 0.02) in genotypes of common SNPs, with most discordance from heterozygous SNPs. Our study demonstrated that SNP array-based GWAS findings were reliable and useful, although only a small portion of genetic variances were explained. NGS can detect not only common but also rare variants, supporting the expectation that NGS-based GWAS will be able to incorporate a much larger portion of genetic variance than SNP arrays-based GWAS.
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Acknowledgements
This research was supported in part by an appointment to the research participation programme at the National Center for Toxicological Research (Wenqian Zhang, Hui Wen Ng and Heng Luo) administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Food and Drugs Administration.
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[Zhang W., Ng H. W., Shu M., Luo H., Su Z., Ge W., Perkins R., Tong W. and Hong H. 2015 Comparing genetic variants detected in the 1000 genomes project with SNPs determined by the International HapMap Consortium. J. Genet. 94, xx–xx
The findings and conclusions in this paper have not been formally disseminated by the US Food and Drug Administration (FDA) and should not be construed to represent the FDA determination or policy
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ZHANG, W., NG, H.W., SHU, M. et al. Comparing genetic variants detected in the 1000 genomes project with SNPs determined by the International HapMap Consortium. J Genet 94, 731–740 (2015). https://doi.org/10.1007/s12041-015-0588-8
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DOI: https://doi.org/10.1007/s12041-015-0588-8