Genotyping and quality controls
All subjects were genotyped with the Korea Biobank Array (referred to as KoreanChip)10. KoreanChip is an Affymerix customized SNP chip optimized for the Korean population and can demonstrate findings from the GWAS of blood biochemical traits. Variants were called by following the Best Practices Steps provided by Affymetrix11, and to minimize the batch effect, we applied the K-medoid algorithm12.
Quality controls of subjects and SNPs were performed with PLINK13 and ONETOOL14. First, we conducted quality controls for each batch. Any SNPs were excluded if any of the following conditions were satisfied: genotype call rates of less than 95% or Hardy-Weinberg equilibrium (HWE) tests15showing P < 1×10-5. In addition, subjects were discarded if the X chromosome homozygosities were between 0.2 and 0.8, genotype call rates were < 95%, or heterozygosity rates of SNPs were outside the average of heterozygosity rate ± 3 standard deviation. Once quality controls were performed for each batch, all batches were pooled, and we performed the same quality control for the pooled samples. Furthermore, for each SNP, we compared the missing rates, HWE, and minor allele frequency (MAF) among batches with Pearson’s chi-square test, and any significant SNPs at the 1×10-5 significance level were excluded. After completing all quality control processes, 8,903 subjects and 649,085 SNPs remained. The detailed procedure is shown in Figure E1.