Abstract
BackgroundWith improvements in genotyping technologies, genome-wide association studies with hundreds of thousands of SNPs allow the identification of candidate genetic loci for multifactorial diseases in different populations. However, genotyping errors caused by genotyping platforms or genotype calling algorithms may lead to inflation of false associations between markers and phenotypes. In addition, the number of SNPs available for genome-wide association studies in the Japanese population has been investigated using only 45 samples in the HapMap project, which could lead to an inaccurate estimation of the number of SNPs with low minor allele frequencies. We genotyped 400 Japanese samples in order to estimate the number of SNPs available for genome-wide association studies in the Japanese population and to examine the performance of the current SNP Array 6.0 platform and the genotype calling algorithm "Birdseed".ResultsAbout 20% of the 909,622 SNP markers on the array were revealed to be monomorphic in the Japanese population. Consequently, 661,599 SNPs were available for genome-wide association studies in the Japanese population, after excluding the poorly behaving SNPs. The Birdseed algorithm accurately determined the genotype calls of each sample with a high overall call rate of over 99.5% and a high concordance rate of over 99.8% using more than 48 samples after removing low-quality samples by adjusting QC criteria.ConclusionOur results confirmed that the SNP Array 6.0 platform reached the level reported by the manufacturer, and thus genome-wide association studies using the SNP Array 6.0 platform have considerable potential to identify candidate susceptibility or resistance genetic factors for multifactorial diseases in the Japanese population, as well as in other populations.
Highlights
With improvements in genotyping technologies, genome-wide association studies with hundreds of thousands of single nucleotide polymorphism (SNP) allow the identification of candidate genetic loci for multifactorial diseases in different populations
When an almost 10-fold excess amount of genomic DNA was used, the average overall call rate drastically decreased to about 80% for both Nsp I and Sty I digestion steps with the Mapping 500 K Array
There was a report that 45% of SNPs observed to be significantly associated with the disease did not agree with Hardy-Weinberg equilibrium (HWE) using the previous version of Mapping 500 K Array set [13]
Summary
With improvements in genotyping technologies, genome-wide association studies with hundreds of thousands of SNPs allow the identification of candidate genetic loci for multifactorial diseases in different populations. The number of SNPs available for genome-wide association studies in the Japanese population has been investigated using only 45 samples in the HapMap project, which could lead to an inaccurate estimation of the number of SNPs with low minor allele frequencies. We genotyped 400 Japanese samples in order to estimate the number of SNPs available for genome-wide association studies in the Japanese population and to examine the performance of the current SNP Array 6.0 platform and the genotype calling algorithm "Birdseed". Over six million SNPs have been uploaded on public SNP databases through the Human Genome Project and international SNP discovery projects Among these SNPs, over 900 K SNPs across the human genome are selected with an average MAF of 19.6%, 18.2% and 20.6% in the HapMap Caucasians, Asians and Africans, respectively, and can be simultaneously genotyped using Affymetrix Genome-Wide Human SNP Array 6.0 platform [9]. The number of genotyped Japanese individuals in the HapMap project was only 45 samples, which may lead to inaccurate estimation of the number of SNPs with low MAF in the Japanese population
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call