Blood Pressure and hypertension are associated with 7 loci in the japanese population

Fumihiko Takeuchi, Masato Isono, Tomohiro Katsuya, Ken Yamamoto, Mitsuhiro Yokota, Takao Sugiyama, Toru Nabika, Akihiro Fujioka, Keizo Ohnaka, Hiroyuki Asano, Yukio Yamori, Shuhei Yamaguchi, Shotai Kobayashi, Ryoichi Takayanagi, Toshio Ogihara, Norihiro Kato

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Abstract

BACKGROUND-: Two consortium-based genome-wide association studies have recently identified robust and significant associations of common variants with systolic and diastolic blood pressures in populations of European descent, warranting further investigation in populations of non-European descent. METHODS AND RESULTS-: We examined the associations at 27 loci reported by the genome-wide association studies on Europeans in a screening panel of Japanese subjects (n=1526) and chose 11 loci showing association signals (1-tailed test in the screening, P<0.3) for an extensive replication study with a follow-up panel of 3 Japanese general-population cohorts (n ≤24 300). Significant associations were replicated for 7 loci-CASZ1, MTHFR, ITGA9, FGF5, CYP17A1-CNNM2, ATP2B1, and CSK-ULK3-with any or all of these 3 traits: systolic blood pressure (P=1.4×10 to 0.05), diastolic blood pressure (P=1.9×10 to 0.05), and hypertension (P=2.0×10 to 0.006; odds ratio, 1.10 to 1.29). The strongest association was observed for FGF5. In the whole study panel, the variance (R) for blood pressure explained by the 7 single-nucleotide polymorphism loci was calculated to be R=0.003 for male and 0.006 for female participants. Stratified analysis implied the potential presence of a gene-age-sex interaction, although it did not reach a conclusive level of statistical significance after adjustment for multiple testing. CONCLUSIONS-: We have confirmed 7 loci associated with blood pressure and/or hypertension in the Japanese. These loci can guide fine-mapping efforts to pinpoint causal variants and causal genes with the integration of multiethnic results.

Original languageEnglish
Pages (from-to)2302-2309
Number of pages8
JournalCirculation
Volume121
Issue number21
DOIs
Publication statusPublished - Jun 1 2010

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Blood Pressure
Hypertension
Population
Genome-Wide Association Study
Genes
Single Nucleotide Polymorphism
Odds Ratio

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Takeuchi, F., Isono, M., Katsuya, T., Yamamoto, K., Yokota, M., Sugiyama, T., ... Kato, N. (2010). Blood Pressure and hypertension are associated with 7 loci in the japanese population. Circulation, 121(21), 2302-2309. https://doi.org/10.1161/CIRCULATIONAHA.109.904664

Blood Pressure and hypertension are associated with 7 loci in the japanese population. / Takeuchi, Fumihiko; Isono, Masato; Katsuya, Tomohiro; Yamamoto, Ken; Yokota, Mitsuhiro; Sugiyama, Takao; Nabika, Toru; Fujioka, Akihiro; Ohnaka, Keizo; Asano, Hiroyuki; Yamori, Yukio; Yamaguchi, Shuhei; Kobayashi, Shotai; Takayanagi, Ryoichi; Ogihara, Toshio; Kato, Norihiro.

In: Circulation, Vol. 121, No. 21, 01.06.2010, p. 2302-2309.

Research output: Contribution to journalArticle

Takeuchi, F, Isono, M, Katsuya, T, Yamamoto, K, Yokota, M, Sugiyama, T, Nabika, T, Fujioka, A, Ohnaka, K, Asano, H, Yamori, Y, Yamaguchi, S, Kobayashi, S, Takayanagi, R, Ogihara, T & Kato, N 2010, 'Blood Pressure and hypertension are associated with 7 loci in the japanese population', Circulation, vol. 121, no. 21, pp. 2302-2309. https://doi.org/10.1161/CIRCULATIONAHA.109.904664
Takeuchi F, Isono M, Katsuya T, Yamamoto K, Yokota M, Sugiyama T et al. Blood Pressure and hypertension are associated with 7 loci in the japanese population. Circulation. 2010 Jun 1;121(21):2302-2309. https://doi.org/10.1161/CIRCULATIONAHA.109.904664
Takeuchi, Fumihiko ; Isono, Masato ; Katsuya, Tomohiro ; Yamamoto, Ken ; Yokota, Mitsuhiro ; Sugiyama, Takao ; Nabika, Toru ; Fujioka, Akihiro ; Ohnaka, Keizo ; Asano, Hiroyuki ; Yamori, Yukio ; Yamaguchi, Shuhei ; Kobayashi, Shotai ; Takayanagi, Ryoichi ; Ogihara, Toshio ; Kato, Norihiro. / Blood Pressure and hypertension are associated with 7 loci in the japanese population. In: Circulation. 2010 ; Vol. 121, No. 21. pp. 2302-2309.
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AU - Takeuchi, Fumihiko

AU - Isono, Masato

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AU - Yokota, Mitsuhiro

AU - Sugiyama, Takao

AU - Nabika, Toru

AU - Fujioka, Akihiro

AU - Ohnaka, Keizo

AU - Asano, Hiroyuki

AU - Yamori, Yukio

AU - Yamaguchi, Shuhei

AU - Kobayashi, Shotai

AU - Takayanagi, Ryoichi

AU - Ogihara, Toshio

AU - Kato, Norihiro

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N2 - BACKGROUND-: Two consortium-based genome-wide association studies have recently identified robust and significant associations of common variants with systolic and diastolic blood pressures in populations of European descent, warranting further investigation in populations of non-European descent. METHODS AND RESULTS-: We examined the associations at 27 loci reported by the genome-wide association studies on Europeans in a screening panel of Japanese subjects (n=1526) and chose 11 loci showing association signals (1-tailed test in the screening, P<0.3) for an extensive replication study with a follow-up panel of 3 Japanese general-population cohorts (n ≤24 300). Significant associations were replicated for 7 loci-CASZ1, MTHFR, ITGA9, FGF5, CYP17A1-CNNM2, ATP2B1, and CSK-ULK3-with any or all of these 3 traits: systolic blood pressure (P=1.4×10 to 0.05), diastolic blood pressure (P=1.9×10 to 0.05), and hypertension (P=2.0×10 to 0.006; odds ratio, 1.10 to 1.29). The strongest association was observed for FGF5. In the whole study panel, the variance (R) for blood pressure explained by the 7 single-nucleotide polymorphism loci was calculated to be R=0.003 for male and 0.006 for female participants. Stratified analysis implied the potential presence of a gene-age-sex interaction, although it did not reach a conclusive level of statistical significance after adjustment for multiple testing. CONCLUSIONS-: We have confirmed 7 loci associated with blood pressure and/or hypertension in the Japanese. These loci can guide fine-mapping efforts to pinpoint causal variants and causal genes with the integration of multiethnic results.

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