Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.
Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.
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DOI：
10.1038/ng.3405
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发表时间：
2015-11
期刊：
影响因子：
30.8
通讯作者：
Chambers JC
中科院分区：
文献类型：
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作者：
Kato N;Loh M;Takeuchi F;Verweij N;Wang X;Zhang W;Kelly TN;Saleheen D;Lehne B;Leach IM;Drong AW;Abbott J;Wahl S;Tan ST;Scott WR;Campanella G;Chadeau-Hyam M;Afzal U;Ahluwalia TS;Bonder MJ;Chen P;Dehghan A;Edwards TL;Esko T;Go MJ;Harris SE;Hartiala J;Kasela S;Kasturiratne A;Khor CC;Kleber ME;Li H;Yu Mok Z;Nakatochi M;Sapari NS;Saxena R;Stewart AFR;Stolk L;Tabara Y;Teh AL;Wu Y;Wu JY;Zhang Y;Aits I;Da Silva Couto Alves A;Das S;Dorajoo R;Hopewell JC;Kim YK;Koivula RW;Luan J;Lyytikäinen LP;Nguyen QN;Pereira MA;Postmus I;Raitakari OT;Scannell Bryan M;Scott RA;Sorice R;Tragante V;Traglia M;White J;Yamamoto K;Zhang Y;Adair LS;Ahmed A;Akiyama K;Asif R;Aung T;Barroso I;Bjonnes A;Braun TR;Cai H;Chang LC;Chen CH;Cheng CY;Chong YS;Collins R;Courtney R;Davies G;Delgado G;Do LD;Doevendans PA;Gansevoort RT;Gao YT;Grammer TB;Grarup N;Grewal J;Gu D;Wander GS;Hartikainen AL;Hazen SL;He J;Heng CK;Hixson JE;Hofman A;Hsu C;Huang W;Husemoen LLN;Hwang JY;Ichihara S;Igase M;Isono M;Justesen JM;Katsuya T;Kibriya MG;Kim YJ;Kishimoto M;Koh WP;Kohara K;Kumari M;Kwek K;Lee NR;Lee J;Liao J;Lieb W;Liewald DCM;Matsubara T;Matsushita Y;Meitinger T;Mihailov E;Milani L;Mills R;Mononen N;Müller-Nurasyid M;Nabika T;Nakashima E;Ng HK;Nikus K;Nutile T;Ohkubo T;Ohnaka K;Parish S;Paternoster L;Peng H;Peters A;Pham ST;Pinidiyapathirage MJ;Rahman M;Rakugi H;Rolandsson O;Ann Rozario M;Ruggiero D;Sala CF;Sarju R;Shimokawa K;Snieder H;Sparsø T;Spiering W;Starr JM;Stott DJ;Stram DO;Sugiyama T;Szymczak S;Tang WHW;Tong L;Trompet S;Turjanmaa V;Ueshima H;Uitterlinden AG;Umemura S;Vaarasmaki M;van Dam RM;van Gilst WH;van Veldhuisen DJ;Viikari JS;Waldenberger M;Wang Y;Wang A;Wilson R;Wong TY;Xiang YB;Yamaguchi S;Ye X;Young RD;Young TL;Yuan JM;Zhou X;Asselbergs FW;Ciullo M;Clarke R;Deloukas P;Franke A;Franks PW;Franks S;Friedlander Y;Gross MD;Guo Z;Hansen T;Jarvelin MR;Jørgensen T;Jukema JW;Kähönen M;Kajio H;Kivimaki M;Lee JY;Lehtimäki T;Linneberg A;Miki T;Pedersen O;Samani NJ;Sørensen TIA;Takayanagi R;Toniolo D;BIOS-consortium;CARDIo GRAMplusCD;LifeLines Cohort Study;InterAct Consortium;Ahsan H;Allayee H;Chen YT;Danesh J;Deary IJ;Franco OH;Franke L;Heijman BT;Holbrook JD;Isaacs A;Kim BJ;Lin X;Liu J;März W;Metspalu A;Mohlke KL;Sanghera DK;Shu XO;van Meurs JBJ;Vithana E;Wickremasinghe AR;Wijmenga C;Wolffenbuttel BHW;Yokota M;Zheng W;Zhu D;Vineis P;Kyrtopoulos SA;Kleinjans JCS;McCarthy MI;Soong R;Gieger C;Scott J;Teo YY;He J;Elliott P;Tai ES;van der Harst P;Kooner JS;Chambers JC
我们在多达320,251名东亚、欧洲和南亚血统的个体中进行了一项跨祖先全基因组血压表型关联和复制研究。我们发现12个新基因座的遗传变异与血压相关（P = 3.9 × 10 - 11至5.0 × 10 - 21）。哨兵血压snp与附近多个CpG位点的DNA甲基化相关，这表明，在一些已鉴定的位点上，DNA甲基化可能位于连接序列变异与血压的调节途径上。12个新位点的前哨snp指向参与血管平滑肌（IGFBP3、KCNK3、PDE3A和PRDM6）和肾脏（ARHGAP24、OSR1、SLC22A7和TBX2）功能的基因。新的和已知的遗传变异预测左心室质量、循环NT-proBNP水平、心血管和全因死亡率增加（P = 0.04至8.6 × 10−6）。我们的研究结果为DNA甲基化在血压调节中的作用提供了新的证据。
We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.