Large-scale genome-wide association studies in east Asians identify new genetic loci influencing metabolic traits

Kim, Young Jin; Go, Min Jin; Hu, Cheng; Hong, Chang Bum; Kim, Yun Kyoung; Lee, Ji Young; Hwang, Joo Yeon; Oh, Ji Hee; Kim, Dong Joon; Kim, Nam Hee; Kim, Soeui; Hong, Eock Kee; Kim, Ji Hyun; Min, Hyun Jin; Kim, Yeonjung; Zhang, Rong; Jia, Weiping; Okada, Yukinori; Takahashi, Atsushi; Kubo, Michiaki; Tanaka, Toshihiro; Kamatani, Naoyuki; Matsuda, Koichi; Park, Taesung; Oh, Bermseok; Kimm, Kuchan; Kang, Daehee; Shin, Chol; Cho, Nam H.; Kim, Hyung Lae; Han, Bok Ghee; Lee, Jong‐Young; Cho, Yoon Shin

doi:10.1038/ng.939

Cited by 262 publications

(275 citation statements)

References 42 publications

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“…The enrichment of markers for the 11q23.3 region (114,600,001-121,300,000 bp as GRCh38) by imputation increased the number of SNPs or single nucleotide variants previous studies have indicated multiple independent susceptibility loci of hypertriglyceridemia ( 13,14 ), and to examine the possibility of the existence of more than one causal variant in this region .…”

Section: Resultsmentioning

confidence: 99%

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Multiple susceptibility loci at chromosome 11q23.3 are associated with plasma triglyceride in East Asians

Bayasgalan

Lee

Kho

et al. 2016

Journal of Lipid Research

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Section: Resultsmentioning

confidence: 99%

“…Serum TG level was measured using standard enzymatic method in a centralized laboratory. Details of the KARE are described in previous reports ( 13,15 ). The genome-wide genetic marker information was available for a total of 8,842 individuals.…”

Section: Subjectsmentioning

confidence: 99%

Multiple susceptibility loci at chromosome 11q23.3 are associated with plasma triglyceride in East Asians

Bayasgalan

Lee

Kho

et al. 2016

Journal of Lipid Research

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“…A recent GWAS performed in East Asians for metabolic traits identified one single-nucleotide polymorphism (SNP), GCKR rs780092 (T-allele), to be associated with higher TG concentrations at the genome-wide significance level [10]. SNP rs780092 was moderately in linkage disequilibrium (LD) with the former identified variants in whites, rs780094 (r 2 =0.50) and rs1260326 (r 2 =0.42) in East Asians.…”

Section: Introductionmentioning

confidence: 99%

Discrete associations of the GCKR variant with metabolic risk in a Chinese population: longitudinal change analysis

Xie

et al. 2015

Diabetologia

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Aims/hypothesis Glucokinase regulatory protein gene (GCKR) variant rs780092 is a novel genetic variant associated with serum triacylglycerol (TG) identified in a genome-wide association study in East Asians. We aimed to investigate associations of rs780092 with incident type 2 diabetes and dyslipidaemia, and the longitudinal changes in glucose and lipid levels. Methods A community-based prospective cohort study was conducted at baseline in 2008, including 5,613 non-diabetic participants (37% male, mean age 57.6 years) with 5 years of follow-up. Blood glucose and lipid was measured at baseline and follow-up. Results Each rs780092 T-allele was associated with a 17% lower risk of incident type 2 diabetes (HR 0.83 [95% CI 0 . 7 3 , 0 . 9 5 ] ) a n d 3 6 % h i g h e r r i s k o f i n c i d e n t hypertriacylglycerolaemia (OR 1.36 [95% CI 1.08, 1.72]), after adjustment for baseline fasting glucose and TG and other confounders. The T-allele was associated with a 5 year increasing level of log 10 TG (β±SE, 0.01±0.004, p=0.005). Mediation analysis showed that both baseline TG and the 5 year increase in log 10 TG were significant mediators in the associations of rs780092 with risk of diabetes. The risk of incident type 2 diabetes associated with 1 SD increase in total and LDL-cholesterol was 35% and 22% lower in TT carriers compared with CC carriers, respectively (both p for interaction≤0.04). Conclusions/interpretation The GCKR rs780092 variant showed opposite-directional associations with type 2 diabetes and hypertriacylglycerolaemia in a Chinese population. Both baseline level and 5 year change in serum TG were mediators of the association between the genetic variant and type 2 diabetes.

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“…The SNP imputation was performed using the IMPUTE program, 11 and the detailed imputation procedure has been published. 12 The International HapMap data from 90 individuals from the JPT and HCB populations were used as a reference panel, 13 with the reference sample size of 90 individuals having more than 95% imputation accuracy. 14 The effect of genotype was computed by linear regression analysis.…”

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Recapitulation of genome-wide association studies on pulse pressure and mean arterial pressure in the Korean population

et al. 2012

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Increased pulse pressure (PP) and decreased mean arterial pressure (MAP) are strong prognostic predictors of adverse cardiovascular events. Recently, the International Consortium for Blood Pressure Genome-Wide Association Studies (ICBP-GWAS) reported eight loci that influenced PP and MAP. The ICBP-GWAS examined 51 cohorts-comprising 122 671 individuals of European ancestry-and identified eight SNPs: five that governed PP and three that controlled MAP. Six of these loci were novel. To replicate these newly identified loci and examine genetic architecture of PP and MAP between European and Asian populations, we conducted a meta-analysis of the eight SNPs combining data from ICBP and general population-based Korean cohorts. Two SNPs (rs13002573 (FIGN) and rs871606 (CHIC2)) for PP and two SNPs (rs1446468 (FIGN) and rs319690 (MAP4)) for MAP were replicated in Koreans. Although our GWAS only found moderate association, we believe that the findings promote us to propose that a similar genetic architecture governs PP and MAP in Asians and Europeans. However, further studies will be needed to confirm the possibility using other Asian population. Keywords: association; ICBP; KoGES; mean arterial pressure; pulse pressure Pulse pressure (PP) is a measure of stiffness in the main arteries, and mean arterial pressure (MAP) is a weighted average of systolic blood pressure (SBP) and diastolic blood pressure (DBP). 1 Increased PP and decreased MAP are strong prognostic predictors of adverse cardiovascular events. 2 Several genetic loci have been reported to be associated with SBP and DBP in Europeans, 3-5 Asians 6-8 and Africans. 9 However, genetic studies on PP and MAP have been limited to those of European ancestry, including a recent report by the International Consortium for Blood Pressure Genome-Wide Association Studies (ICBP-GWAS). 10 The ICBP-GWAS reported five loci for PP and three loci for MAP. Four (CHIC2, PIK3CG, NOV and ADAMTS8) of the PP loci and two (MAP4 and ADRB1) of the MAP loci were novel. 10 The remaining locus (FIGN) that was associated with both PP and MAP was recently associated with SBP in a meta-analysis of Asians. 8 In this study, we conducted an association analysis of the SNPs that were reported by the ICBP-GWAS in 7551 Koreans using data from KARE, an earlier GWAS in Koreans. The subjects and their genotypes in the original study have been reported. 6 In brief, the 7551 individuals were recruited as population-based cohorts in the Korean Genome and Epidemiology Study (KoGES), residing in KyungGi-Do province, near Seoul, Korea. This study was approved by the Institutional Review Board of the Korea National Institute of Health, and each participant provided written informed consent for participation.Blood pressure measurements were taken three times in the supine position. Before the first measurement, the participants rested for 5 min, and three measurements were taken at least 30 s apart. The average of the three measurements was used for this study. PP was defined as SBP -DBP, and MAP was defined as ...

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Large-scale genome-wide association studies in east Asians identify new genetic loci influencing metabolic traits

Cited by 262 publications

References 42 publications

Multiple susceptibility loci at chromosome 11q23.3 are associated with plasma triglyceride in East Asians

Multiple susceptibility loci at chromosome 11q23.3 are associated with plasma triglyceride in East Asians

Discrete associations of the GCKR variant with metabolic risk in a Chinese population: longitudinal change analysis

Recapitulation of genome-wide association studies on pulse pressure and mean arterial pressure in the Korean population

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