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Genome-wide association study meta-analysis reveals transethnic replication of mean arterial and pulse pressure loci.

Kelly TN, Takeuchi F, Tabara Y, Edwards TL, Kim YJ, Chen P, Li H, Wu Y, Yang CF, Zhang Y, Gu D, Katsuya T, Ohkubo T, Gao YT, Go MJ, Teo YY, Lu L, Lee NR, Chang LC, Peng H, Zhao Q, Nakashima E, Kita Y, Shu XO, Kim NH, Tai ES, Wang Y, Adair LS, Chen CH, Zhang S, Li C, Nabika T, Umemura S, Cai Q, Cho YS, Wong TY, Zhu J, Wu JY, Gao X, Hixson JE, Cai H, Lee J, Cheng CY, Rao DC, Xiang YB, Cho MC, Han BG, Wang A, Tsai FJ, Mohlke K, Lin X, Ikram MK, Lee JY, Zheng W, Tetsuro M, Kato N, He J
Hypertension. 2013 62 (5): 853-9

PMID: 24001895 · PMCID: PMC3972802 · DOI:10.1161/HYPERTENSIONAHA.113.01148

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<5.0×10(-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<1.4×10(-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=7.5×10(-15)), rs2681492 at ATP2B1 (P=3.4×10(-7)), rs11191593 at NT5C2 (1.1×10(-6)), rs3824755 at CYP17A1 (P=1.2×10(-6)), and rs13149993 at FGF5 (P=2.4×10(-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=1.2×10(-5)) and rs11191593 at NT5C2 (P=1.1×10(-3)), with suggestive evidence of replication among an additional 2 variants including rs3824755 at CYP17A1 (P=6.1×10(-3)) and rs2681492 at ATP2B1 (P=9.0×10(-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.

MeSH Terms (12)

Adult Arterial Pressure Asian Continental Ancestry Group Blood Pressure Female Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study Humans Hypertension Male Polymorphism, Single Nucleotide

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