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

2019; Nature Portfolio; Volume: 9; Issue: 1 Linguagem: Inglês

10.1038/s41598-018-37832-9

2045-2322

Sanghoon Moon, Young Jin Kim, Sohee Han, Mi Yeong Hwang, Dong Mun Shin, Min Young Park, Yontao Lu, Kyungheon Yoon, Hye-Mi Jang, Yun Kyoung Kim, Tae Joo Park, Dae Sub Song, Jae Kyung Park, Jong‐Eun Lee, Bong-Jo Kim,

Genetic Syndromes and Imprinting

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.