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

Yoon Shin Cho; Min Jin Go; Young Jin Kim; Jee Yeon Heo; Ji Hee Oh; Hyo Jeong Ban; Dankyu Yoon; Mi Hee Lee; Dong Joon Kim; Miey Park; Seung Hun Cha; Jun Woo Kim; Bok Ghee Han; Haesook Min; Younjhin Ahn; Man Suk Park; Hye Ree Han; Hye Yoon Jang; Eun Young Cho; Jong Eun Lee; Nam H. Cho; Chol Shin; Taesung Park; Ji Wan Park; Jong Keuk Lee; Lon Cardon; Geraldine Clarke; Mark I. McCarthy; Jong Young Lee; Jong Koo Lee; Bermseok Oh; Hyung Lae Kim

doi:10.1038/ng.357

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

Yoon Shin Cho, Min Jin Go, Young Jin Kim, Jee Yeon Heo, Ji Hee Oh, Hyo Jeong Ban, Dankyu Yoon, Mi Hee Lee, Dong Joon Kim, Miey Park, Seung Hun Cha, Jun Woo Kim, Bok Ghee Han, Haesook Min, Younjhin Ahn, Man Suk Park, Hye Ree Han, Hye Yoon Jang, Eun Young Cho, Jong Eun LeeNam H. Cho, Chol Shin, Taesung Park, Ji Wan Park, Jong Keuk Lee, Lon Cardon, Geraldine Clarke, Mark I. McCarthy, Jong Young Lee, Jong Koo Lee, Bermseok Oh, Hyung Lae Kim

Department of Biochemistry

Research output: Contribution to journal › Article › peer-review

810 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	527-534
Number of pages	8
Journal	Nature Genetics
Volume	41
Issue number	5
DOIs	https://doi.org/10.1038/ng.357
State	Published - May 2009

Bibliographical note

Funding Information:
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).

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Cho, Y. S., Go, M. J., Kim, Y. J., Heo, J. Y., Oh, J. H., Ban, H. J., Yoon, D., Lee, M. H., Kim, D. J., Park, M., Cha, S. H., Kim, J. W., Han, B. G., Min, H., Ahn, Y., Park, M. S., Han, H. R., Jang, H. Y., Cho, E. Y., ... Kim, H. L. (2009). A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nature Genetics, 41(5), 527-534. https://doi.org/10.1038/ng.357

@article{49ca731892654acfbe4f4cf79394f90d,

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

abstract = "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.",

author = "Cho, {Yoon Shin} and Go, {Min Jin} and Kim, {Young Jin} and Heo, {Jee Yeon} and Oh, {Ji Hee} and Ban, {Hyo Jeong} and Dankyu Yoon and Lee, {Mi Hee} and Kim, {Dong Joon} and Miey Park and Cha, {Seung Hun} and Kim, {Jun Woo} and Han, {Bok Ghee} and Haesook Min and Younjhin Ahn and Park, {Man Suk} and Han, {Hye Ree} and Jang, {Hye Yoon} and Cho, {Eun Young} and Lee, {Jong Eun} and Cho, {Nam H.} and Chol Shin and Taesung Park and Park, {Ji Wan} and Lee, {Jong Keuk} and Lon Cardon and Geraldine Clarke and McCarthy, {Mark I.} and Lee, {Jong Young} and Lee, {Jong Koo} and Bermseok Oh and Kim, {Hyung Lae}",

note = "Funding Information: 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).",

year = "2009",

month = may,

doi = "10.1038/ng.357",

language = "English",

volume = "41",

pages = "527--534",

journal = "Nature Genetics",

issn = "1061-4036",

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Cho, YS, Go, MJ, Kim, YJ, Heo, JY, Oh, JH, Ban, HJ, Yoon, D, Lee, MH, Kim, DJ, Park, M, Cha, SH, Kim, JW, Han, BG, Min, H, Ahn, Y, Park, MS, Han, HR, Jang, HY, Cho, EY, Lee, JE, Cho, NH, Shin, C, Park, T, Park, JW, Lee, JK, Cardon, L, Clarke, G, McCarthy, MI, Lee, JY, Lee, JK, Oh, B & Kim, HL 2009, 'A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits', Nature Genetics, vol. 41, no. 5, pp. 527-534. https://doi.org/10.1038/ng.357

TY - JOUR

T1 - A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits

AU - Cho, Yoon Shin

AU - Go, Min Jin

AU - Kim, Young Jin

AU - Heo, Jee Yeon

AU - Oh, Ji Hee

AU - Ban, Hyo Jeong

AU - Yoon, Dankyu

AU - Lee, Mi Hee

AU - Kim, Dong Joon

AU - Park, Miey

AU - Cha, Seung Hun

AU - Kim, Jun Woo

AU - Han, Bok Ghee

AU - Min, Haesook

AU - Ahn, Younjhin

AU - Park, Man Suk

AU - Han, Hye Ree

AU - Jang, Hye Yoon

AU - Cho, Eun Young

AU - Lee, Jong Eun

AU - Cho, Nam H.

AU - Shin, Chol

AU - Park, Taesung

AU - Park, Ji Wan

AU - Lee, Jong Keuk

AU - Cardon, Lon

AU - Clarke, Geraldine

AU - McCarthy, Mark I.

AU - Lee, Jong Young

AU - Lee, Jong Koo

AU - Oh, Bermseok

AU - Kim, Hyung Lae

N1 - Funding Information: 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).

PY - 2009/5

Y1 - 2009/5

N2 - 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.

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

Abstract

Bibliographical note

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