The Korea Biobank Array: Design and Identification of Coding Variants Associated with Blood Biochemical Traits

Abstract

We introduce the design and implementation of a new array, the Korea Biobank Array (referred to as KoreanChip), optimized for the Korean population and demonstrate findings from GWAS of blood biochemical traits. KoreanChip comprised >833,000 markers including >247,000 rare-frequency or functional variants estimated from >2,500 sequencing data in Koreans. Of the 833 K markers, 208 K functional markers were directly genotyped. Particularly, >89 K markers were presented in East Asians. KoreanChip achieved higher imputation performance owing to the excellent genomic coverage of 95.38% for common and 73.65% for low-frequency variants. From GWAS (Genome-wide association study) using 6,949 individuals, 28 associations were successfully recapitulated. Moreover, 9 missense variants were newly identified, of which we identified new associations between a common population-specific missense variant, rs671 (p.Glu457Lys) of ALDH2, and two traits including aspartate aminotransferase (P = 5.20 × 10−13) and alanine aminotransferase (P = 4.98 × 10−8). Furthermore, two novel missense variants of GPT with rare frequency in East Asians but extreme rarity in other populations were associated with alanine aminotransferase (rs200088103; p.Arg133Trp, P = 2.02 × 10−9 and rs748547625; p.Arg143Cys, P = 1.41 × 10−6). These variants were successfully replicated in 6,000 individuals (P = 5.30 × 10−8 and P = 1.24 × 10−6). GWAS results suggest the promising utility of KoreanChip with a substantial number of damaging variants to identify new population-specific disease-associated rare/functional variants.

Genome‐wide interaction study of single‐nucleotide polymorphisms and alcohol consumption on blood pressure: The Ansan and Ansung study of the Korean Genome and Epidemiology Study (KoGES)

“…The genotype data for the HEXA replication set was generated by the Korean Chip (K‐CHIP), an SNP array optimized for the Korean population including a total of 833,535 SNPs and insertion‐deletion (indel) markers. Imputation and QC procedures were similar to the present study (Moon et al, 2019).…”

Role of aldehyde dehydrogenases, alcohol dehydrogenase 1B genotype, alcohol consumption, and their combination in breast cancer in East-Asian women

“…The Korea Biobank Array is a chip optimized for genetic studies in the Korean population. Full details on Korea Biobank Array are described elsewhere 39,40 . Of the 750 breast cancer cases and 3977 controls, 5 cases were excluded owing to a low call rate of <97% (n = 1) and family relationships (n = 4); after quality control, 745 cases and 3977 controls were evaluated.…”

Identification of type 2 diabetes loci in 433,540 East Asian individuals

“…The East Asian type 2 diabetes (T2D) meta-analyses were performed with studies participating in the Asian Genetic Epidemiology Network (AGEN), a consortium of genetic epidemiology studies of T2D and related traits conducted in individuals of East Asian ancestry, and the Diabetes Meta-analysis of Trans-ethnic Association Studies (DIAMANTE), a consortium examining the genetic contribution to T2D across diverse ancestry populations including African-American, East Asian, European, Hispanic, and South Asian. The East Asian meta-analysis included 77,418 T2D cases and 356,122 controls from 23 GWAS, including three biobanks, CKB, KBA 52,53 , and BBJ 4 [effective sample size (N eff ) = 211,793; Supplementary Figure 1]. A subset of studies was analyzed in BMI-adjusted and sex-specific models (54,481 cases, 224,231 cases; N eff = 135,780).…”

“…To detect multiple distinct association signals at each associated locus, we combined overlapping loci when the distance between any pair of lead variants was <1 Mb. We then performed approximate conditional analyses using GCTA 8 with genome-wide meta-analysis summary statistics and LD estimated from 78,000 samples from the Korean Biobank Array 53 .…”