Interethnic analyses of blood pressure loci in populations of East Asian and European descent

Fumihiko Takeuchi; Masato Akiyama; Nana Matoba; Tomohiro Katsuya; Masahiro Nakatochi; Yasuharu Tabara; Akira Narita; Woei-Yuh Saw; Sanghoon Moon; Cassandra N. Spracklen; Jin-Fang Chai; Young-Jin Kim; Liang Zhang; Chaolong Wang; Huaixing Li; Honglan Li; Jer-Yuarn Wu; Rajkumar Dorajoo; Jovia L. Nierenberg; Ya Xing Wang; Jing He; Derrick A. Bennett; Atsushi Takahashi; Yukihide Momozawa; Makoto Hirata; Koichi Matsuda; Hiromi Rakugi; Eitaro Nakashima; Masato Isono; Matsuyuki Shirota; Atsushi Hozawa; Sahoko Ichihara; Tatsuaki Matsubara; Ken Yamamoto; Katsuhiko Kohara; Michiya Igase; Sohee Han; Penny Gordon-Larsen; Wei Huang; Nanette R. Lee; Linda S. Adair; Mi Yeong Hwang; Juyoung Lee; Miao Li Chee; Charumathi Sabanayagam; Wanting Zhao; Jianjun Liu; Dermot F. Reilly; Liang Sun; Shaofeng Huo; Joseph Kleinjans; International Genomics of Blood Pressure (iGEN-BP) Consortium

doi:10.1038/s41467-018-07345-0

Interethnic analyses of blood pressure loci in populations of East Asian and European descent

Fumihiko Takeuchi, Masato Akiyama, Nana Matoba, Tomohiro Katsuya, Masahiro Nakatochi^*, Yasuharu Tabara, Akira Narita, Woei-Yuh Saw, Sanghoon Moon, Cassandra N. Spracklen, Jin-Fang Chai, Young-Jin Kim, Liang Zhang, Chaolong Wang, Huaixing Li, Honglan Li, Jer-Yuarn Wu, Rajkumar Dorajoo, Jovia L. Nierenberg, Ya Xing WangJing He, Derrick A. Bennett, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Koichi Matsuda, Hiromi Rakugi, Eitaro Nakashima, Masato Isono, Matsuyuki Shirota, Atsushi Hozawa, Sahoko Ichihara, Tatsuaki Matsubara, Ken Yamamoto, Katsuhiko Kohara, Michiya Igase, Sohee Han, Penny Gordon-Larsen, Wei Huang, Nanette R. Lee, Linda S. Adair, Mi Yeong Hwang, Juyoung Lee, Miao Li Chee, Charumathi Sabanayagam, Wanting Zhao, Jianjun Liu, Dermot F. Reilly, Liang Sun, Shaofeng Huo, Joseph Kleinjans, International Genomics of Blood Pressure (iGEN-BP) Consortium

^*Corresponding author for this work

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

Abstract

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP ( max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.

Original language	English
Article number	5052
Pages (from-to)	1-16
Number of pages	16
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-07345-0
Publication status	Published - 28 Nov 2018

Keywords

GENOME-WIDE ASSOCIATION
BODY-MASS INDEX
LINKAGE DISEQUILIBRIUM
CARDIOVASCULAR-DISEASE
FUNCTIONAL ANNOTATION
RARE VARIANTS
COMMON
METAANALYSIS
HERITABILITY
ARCHITECTURE

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Cite this

Takeuchi, F., Akiyama, M., Matoba, N., Katsuya, T., Nakatochi, M., Tabara, Y., Narita, A., Saw, W.-Y., Moon, S., Spracklen, C. N., Chai, J.-F., Kim, Y.-J., Zhang, L., Wang, C., Li, H., Li, H., Wu, J.-Y., Dorajoo, R., Nierenberg, J. L., ... International Genomics of Blood Pressure (iGEN-BP) Consortium (2018). Interethnic analyses of blood pressure loci in populations of East Asian and European descent. Nature Communications, 9, 1-16. Article 5052. https://doi.org/10.1038/s41467-018-07345-0

@article{191ee955222a41408abafa105fb43247,

title = "Interethnic analyses of blood pressure loci in populations of East Asian and European descent",

abstract = "Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP ( max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.",

keywords = "GENOME-WIDE ASSOCIATION, BODY-MASS INDEX, LINKAGE DISEQUILIBRIUM, CARDIOVASCULAR-DISEASE, FUNCTIONAL ANNOTATION, RARE VARIANTS, COMMON, METAANALYSIS, HERITABILITY, ARCHITECTURE",

author = "Fumihiko Takeuchi and Masato Akiyama and Nana Matoba and Tomohiro Katsuya and Masahiro Nakatochi and Yasuharu Tabara and Akira Narita and Woei-Yuh Saw and Sanghoon Moon and Spracklen, {Cassandra N.} and Jin-Fang Chai and Young-Jin Kim and Liang Zhang and Chaolong Wang and Huaixing Li and Honglan Li and Jer-Yuarn Wu and Rajkumar Dorajoo and Nierenberg, {Jovia L.} and Wang, {Ya Xing} and Jing He and Bennett, {Derrick A.} and Atsushi Takahashi and Yukihide Momozawa and Makoto Hirata and Koichi Matsuda and Hiromi Rakugi and Eitaro Nakashima and Masato Isono and Matsuyuki Shirota and Atsushi Hozawa and Sahoko Ichihara and Tatsuaki Matsubara and Ken Yamamoto and Katsuhiko Kohara and Michiya Igase and Sohee Han and Penny Gordon-Larsen and Wei Huang and Lee, {Nanette R.} and Adair, {Linda S.} and Hwang, {Mi Yeong} and Juyoung Lee and Chee, {Miao Li} and Charumathi Sabanayagam and Wanting Zhao and Jianjun Liu and Reilly, {Dermot F.} and Liang Sun and Shaofeng Huo and Joseph Kleinjans and {International Genomics of Blood Pressure (iGEN-BP) Consortium}",

year = "2018",

month = nov,

day = "28",

doi = "10.1038/s41467-018-07345-0",

language = "English",

volume = "9",

pages = "1--16",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Takeuchi, F, Akiyama, M, Matoba, N, Katsuya, T, Nakatochi, M, Tabara, Y, Narita, A, Saw, W-Y, Moon, S, Spracklen, CN, Chai, J-F, Kim, Y-J, Zhang, L, Wang, C, Li, H, Li, H, Wu, J-Y, Dorajoo, R, Nierenberg, JL, Wang, YX, He, J, Bennett, DA, Takahashi, A, Momozawa, Y, Hirata, M, Matsuda, K, Rakugi, H, Nakashima, E, Isono, M, Shirota, M, Hozawa, A, Ichihara, S, Matsubara, T, Yamamoto, K, Kohara, K, Igase, M, Han, S, Gordon-Larsen, P, Huang, W, Lee, NR, Adair, LS, Hwang, MY, Lee, J, Chee, ML, Sabanayagam, C, Zhao, W, Liu, J, Reilly, DF, Sun, L, Huo, S, Kleinjans, J & International Genomics of Blood Pressure (iGEN-BP) Consortium 2018, 'Interethnic analyses of blood pressure loci in populations of East Asian and European descent', Nature Communications, vol. 9, 5052, pp. 1-16. https://doi.org/10.1038/s41467-018-07345-0

TY - JOUR

T1 - Interethnic analyses of blood pressure loci in populations of East Asian and European descent

AU - Takeuchi, Fumihiko

AU - Akiyama, Masato

AU - Matoba, Nana

AU - Katsuya, Tomohiro

AU - Nakatochi, Masahiro

AU - Tabara, Yasuharu

AU - Narita, Akira

AU - Saw, Woei-Yuh

AU - Moon, Sanghoon

AU - Spracklen, Cassandra N.

AU - Chai, Jin-Fang

AU - Kim, Young-Jin

AU - Zhang, Liang

AU - Wang, Chaolong

AU - Li, Huaixing

AU - Li, Honglan

AU - Wu, Jer-Yuarn

AU - Dorajoo, Rajkumar

AU - Nierenberg, Jovia L.

AU - Wang, Ya Xing

AU - He, Jing

AU - Bennett, Derrick A.

AU - Takahashi, Atsushi

AU - Momozawa, Yukihide

AU - Hirata, Makoto

AU - Matsuda, Koichi

AU - Rakugi, Hiromi

AU - Nakashima, Eitaro

AU - Isono, Masato

AU - Shirota, Matsuyuki

AU - Hozawa, Atsushi

AU - Ichihara, Sahoko

AU - Matsubara, Tatsuaki

AU - Yamamoto, Ken

AU - Kohara, Katsuhiko

AU - Igase, Michiya

AU - Han, Sohee

AU - Gordon-Larsen, Penny

AU - Huang, Wei

AU - Lee, Nanette R.

AU - Adair, Linda S.

AU - Hwang, Mi Yeong

AU - Lee, Juyoung

AU - Chee, Miao Li

AU - Sabanayagam, Charumathi

AU - Zhao, Wanting

AU - Liu, Jianjun

AU - Reilly, Dermot F.

AU - Sun, Liang

AU - Huo, Shaofeng

AU - Kleinjans, Joseph

AU - International Genomics of Blood Pressure (iGEN-BP) Consortium

PY - 2018/11/28

Y1 - 2018/11/28

N2 - Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP ( max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.

AB - Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP ( max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.

KW - GENOME-WIDE ASSOCIATION

KW - BODY-MASS INDEX

KW - LINKAGE DISEQUILIBRIUM

KW - CARDIOVASCULAR-DISEASE

KW - FUNCTIONAL ANNOTATION

KW - RARE VARIANTS

KW - COMMON

KW - METAANALYSIS

KW - HERITABILITY

KW - ARCHITECTURE

U2 - 10.1038/s41467-018-07345-0

DO - 10.1038/s41467-018-07345-0

M3 - Article

C2 - 30487518

SN - 2041-1723

VL - 9

SP - 1

EP - 16

JO - Nature Communications

JF - Nature Communications

M1 - 5052

ER -