A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits

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To identify genetic factors influencing quantitative traits of biomedical importance, we conducted a genome-wide association study in 8,842 samples from population-based cohorts recruited in Korea. For height and body mass index, most variants detected overlapped those reported in European samples. For the other traits examined, replication of promising GWAS signals in 7,861 independent Korean samples identified six previously unknown loci. For pulse rate, signals reaching genome-wide significance mapped to chromosomes 1q32 (rs12731740, P = 2.9 × 10−9) and 6q22 (rs12110693, P = 1.6 × 10−9), with the latter 400 kb from the coding sequence of GJA1. For systolic blood pressure, the most compelling association involved chromosome 12q21 and variants near the ATP2B1 gene (rs17249754, P = 1.3 × 10−7). For waist-hip ratio, variants on chromosome 12q24 (rs2074356, P = 7.8 × 10−12) showed convincing associations, although no regional transcript has strong biological candidacy. Finally, we identified two loci influencing bone mineral density at multiple sites. On chromosome 7q31, rs7776725 (within the FAM3C gene) was associated with bone density at the radius (P = 1.0 × 10−11), tibia (P = 1.6 × 10−6) and heel (P = 1.9 × 10−10). On chromosome 7p14, rs1721400 (mapping close to SFRP4, a frizzled protein gene) showed consistent associations at the same three sites (P = 2.2 × 10−3, P = 1.4 × 10−7 and P = 6.0 × 10−4, respectively). This large-scale GWA analysis of well-characterized Korean population-based samples highlights previously unknown biological pathways.

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Figure 1: Comparison of genetic background between subjects from Ansung and Ansan cohorts.
Figure 2: Quantile-quantile plots for the eight quantitative traits.
Figure 3: Six newly identified loci showing strong evidence of association.


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This work was supported by a grant from the Ministry for Health, Welfare and Family Affairs, Republic of Korea (4845-301-430-260-00), and an intramural grant from the Korea National Institute of Health, Korea Center for Disease Control, Republic of Korea (4845-301-430-210-13).

Author information

The study was designed by H-.L.K., B.O., J-.K.L. and J-.Y.L. Genotyping experiments were performed by J-.E.L., J.H.O., D-.J.K., M.P., S-.H.C., H-.Y.J. and E.Y.C. DNA sample preparation was carried out by M.H.L., J-.W.K. and B-.G.H. Phenotype information was collected by H.M., Y.A., M.S.P., N.H.C. and C.S. Statistical analysis was performed by M.J.G., D.Y., H.R.H., T.P., G.C. and Y.S.C. Bioinformatic analysis was conducted by Y.J.K., J.Y.H., H-.J.B., L.C. and Y.S.C. The manuscript was written by Y.S.C., B.O., J.W.P., J-.K.L., M.I.M. and H-.L.K. All authors reviewed the manuscript.

Correspondence to Bermseok Oh or Hyung-Lae Kim.

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Supplementary Figures 1–8, Supplementary Tables 1–9, Supplementary Methods (PDF 3008 kb)

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