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 language | English |
|---|---|
| Pages (from-to) | 2302-2309 |
| Number of pages | 8 |
| Journal | Circulation |
| Volume | 121 |
| Issue number | 21 |
| DOIs | |
| Publication status | Published - Jun 1 2010 |
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All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
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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 journal › Article
}
TY - JOUR
T1 - Blood Pressure and hypertension are associated with 7 loci in the japanese population
AU - Takeuchi, Fumihiko
AU - Isono, Masato
AU - Katsuya, Tomohiro
AU - Yamamoto, Ken
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
PY - 2010/6/1
Y1 - 2010/6/1
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.
AB - 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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U2 - 10.1161/CIRCULATIONAHA.109.904664
DO - 10.1161/CIRCULATIONAHA.109.904664
M3 - Article
C2 - 20479155
AN - SCOPUS:77953230966
VL - 121
SP - 2302
EP - 2309
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 21
ER -