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.