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Genome-Wide Association Study Meta-Analysis Reveals Transethnic Replication of Mean Arterial and Pulse Pressure Loci

Kelly, Tanika N.; Takeuchi, Fumihiko; Tabara, Yasuharu; Edwards, Todd L.; Kim, Young Jin; Chen, Peng; Li, Huaixing; Wu, Ying; Yang, Chi-Fan; Zhang, Yonghong; Gu, Dongfeng; Katsuya, Tomohiro; Ohkubo, Takayoshi; Gao, Yu-Tang; Go, Min Jin; Teo, Yik Ying; Lu, Ling; Lee, Nanette R.; Chang, Li-Ching; Peng, Hao; Zhao, Qi; Nakashima, Eitaro; Kita, Yoshikuni; Shu, Xiao-Ou; Kim, Nam Hee; Tai, E. Shyong; Wang, Yiqin; Adair, Linda S.; Chen, Chien-Hsiun; Zhang, Shihiu; Li, Changwei; Nabika, Toru; Umemura, Satoshi; Cai, Qiuyin; Cho, Yoon Shin; Wong, Tien Yin; Zhu, Jingwen; Wu, Jer-Yuarn; Gao, Xin; Hixson, James E.; Cai, Hui; Lee, Juyoung; Cheng, Ching-Yu; Rao, Dabeeru C.; Xiang, Yong-Bing; Cho, Myeong-Chan; Han, Bok-Ghee; Wang, Aili; Tsai, Fuu-Jen; Mohlke, Karen L.; Lin, Xu; Ikram, Mohammad Kamran; Lee, Jong-Young; Zheng, Wei; Tetsuro, Miki; Kato, Norihiro; & He, Jiang. (2013). Genome-Wide Association Study Meta-Analysis Reveals Transethnic Replication of Mean Arterial and Pulse Pressure Loci. Hypertension, 62(5), 853-9. PMCID: PMC3972802

Kelly, Tanika N.; Takeuchi, Fumihiko; Tabara, Yasuharu; Edwards, Todd L.; Kim, Young Jin; Chen, Peng; Li, Huaixing; Wu, Ying; Yang, Chi-Fan; Zhang, Yonghong; Gu, Dongfeng; Katsuya, Tomohiro; Ohkubo, Takayoshi; Gao, Yu-Tang; Go, Min Jin; Teo, Yik Ying; Lu, Ling; Lee, Nanette R.; Chang, Li-Ching; Peng, Hao; Zhao, Qi; Nakashima, Eitaro; Kita, Yoshikuni; Shu, Xiao-Ou; Kim, Nam Hee; Tai, E. Shyong; Wang, Yiqin; Adair, Linda S.; Chen, Chien-Hsiun; Zhang, Shihiu; Li, Changwei; Nabika, Toru; Umemura, Satoshi; Cai, Qiuyin; Cho, Yoon Shin; Wong, Tien Yin; Zhu, Jingwen; Wu, Jer-Yuarn; Gao, Xin; Hixson, James E.; Cai, Hui; Lee, Juyoung; Cheng, Ching-Yu; Rao, Dabeeru C.; Xiang, Yong-Bing; Cho, Myeong-Chan; Han, Bok-Ghee; Wang, Aili; Tsai, Fuu-Jen; Mohlke, Karen L.; Lin, Xu; Ikram, Mohammad Kamran; Lee, Jong-Young; Zheng, Wei; Tetsuro, Miki; Kato, Norihiro; & He, Jiang. (2013). Genome-Wide Association Study Meta-Analysis Reveals Transethnic Replication of Mean Arterial and Pulse Pressure Loci. Hypertension, 62(5), 853-9. PMCID: PMC3972802

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We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26 600 East Asian participants (stage 1) followed by replication study of up to 28 783 participants (stage 2). For novel loci, statistical significance was determined by a P<5.0x10(-8) in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replication was determined by consistency in effect direction and a Bonferroni-corrected P<1.4x10(-3). No novel loci were identified by the current study. Five independent mean arterial pressure variants demonstrated robust evidence for transethnic replication including rs17249754 at ATP2B1 (P=7.5x10(-15)), rs2681492 at ATP2B1 (P=3.4x10(-7)), rs11191593 at NT5C2 (1.1x10(-6)), rs3824755 at CYP17A1 (P=1.2x10(-6)), and rs13149993 at FGF5 (P=2.4x10(-4)). Two additional variants showed suggestive evidence of transethnic replication (consistency in effect direction and P<0.05), including rs319690 at MAP4 (P=0.014) and rs1173771 at NPR3 (P=0.018). For pulse pressure, robust evidence of replication was identified for 2 independent variants, including rs17249754 at ATP2B1 (P=1.2x10(-5)) and rs11191593 at NT5C2 (P=1.1x10(-3)), with suggestive evidence of replication among an additional 2 variants including rs3824755 at CYP17A1 (P=6.1x10(-3)) and rs2681492 at ATP2B1 (P=9.0x10(-3)). Replicated variants demonstrated consistency in effect sizes between East Asian and European samples, with effect size differences ranging from 0.03 to 0.24 mm Hg for mean arterial pressure and from 0.03 to 0.21 mm Hg for pulse pressure. In conclusion, we present the first evidence of transethnic replication of several mean arterial and pulse pressure loci in an East Asian population.




JOUR



Kelly, Tanika N.
Takeuchi, Fumihiko
Tabara, Yasuharu
Edwards, Todd L.
Kim, Young Jin
Chen, Peng
Li, Huaixing
Wu, Ying
Yang, Chi-Fan
Zhang, Yonghong
Gu, Dongfeng
Katsuya, Tomohiro
Ohkubo, Takayoshi
Gao, Yu-Tang
Go, Min Jin
Teo, Yik Ying
Lu, Ling
Lee, Nanette R.
Chang, Li-Ching
Peng, Hao
Zhao, Qi
Nakashima, Eitaro
Kita, Yoshikuni
Shu, Xiao-Ou
Kim, Nam Hee
Tai, E. Shyong
Wang, Yiqin
Adair, Linda S.
Chen, Chien-Hsiun
Zhang, Shihiu
Li, Changwei
Nabika, Toru
Umemura, Satoshi
Cai, Qiuyin
Cho, Yoon Shin
Wong, Tien Yin
Zhu, Jingwen
Wu, Jer-Yuarn
Gao, Xin
Hixson, James E.
Cai, Hui
Lee, Juyoung
Cheng, Ching-Yu
Rao, Dabeeru C.
Xiang, Yong-Bing
Cho, Myeong-Chan
Han, Bok-Ghee
Wang, Aili
Tsai, Fuu-Jen
Mohlke, Karen L.
Lin, Xu
Ikram, Mohammad Kamran
Lee, Jong-Young
Zheng, Wei
Tetsuro, Miki
Kato, Norihiro
He, Jiang



2013


Hypertension

62

5

853-9







10.1161/hypertensionaha.113.01148

PMC3972802


33