Kraja Aldi T, Cook James P, Warren Helen R, Surendran Praveen, Liu Chunyu, Evangelou Evangelos, Manning Alisa K, Grarup Niels, Drenos Fotios, Sim Xueling, Smith Albert Vernon, Amin Najaf, Blakemore Alexandra I F, Bork-Jensen Jette, Brandslund Ivan, Farmaki Aliki-Eleni, Fava Cristiano, Ferreira Teresa, Herzig Karl-Heinz, Giri Ayush, Giulianini Franco, Grove Megan L, Guo Xiuqing, Harris Sarah E, Have Christian T, Havulinna Aki S, Zhang He, Jørgensen Marit E, Käräjämäki AnneMari, Kooperberg Charles, Linneberg Allan, Little Louis, Liu Yongmei, Bonnycastle Lori L, Lu Yingchang, Mägi Reedik, Mahajan Anubha, Malerba Giovanni, Marioni Riccardo E, Mei Hao, Menni Cristina, Morrison Alanna C, Padmanabhan Sandosh, Palmas Walter, Poveda Alaitz, Rauramaa Rainer, Rayner Nigel William, Riaz Muhammad, Rice Ken, Richard Melissa A, Smith Jennifer A, Southam Lorraine, Stančáková Alena, Stirrups Kathleen E, Tragante Vinicius, Tuomi Tiinamaija, Tzoulaki Ioanna, Varga Tibor V, Weiss Stefan, Yiorkas Andrianos M, Young Robin, Zhang Weihua, Barnes Michael R, Cabrera Claudia P, Gao He, Boehnke Michael, Boerwinkle Eric, Chambers John C, Connell John M, Christensen Cramer K, de Boer Rudolf A, Deary Ian J, Dedoussis George, Deloukas Panos, Dominiczak Anna F, Dörr Marcus, Joehanes Roby, Edwards Todd L, Esko Tõnu, Fornage Myriam, Franceschini Nora, Franks Paul W, Gambaro Giovanni, Groop Leif, Hallmans Göran, Hansen Torben, Hayward Caroline, Heikki Oksa, Ingelsson Erik, Tuomilehto Jaakko, Jarvelin Marjo-Riitta, Kardia Sharon L R, Karpe Fredrik, Kooner Jaspal S, Lakka Timo A, Langenberg Claudia, Lind Lars, Loos Ruth J F, Laakso Markku, McCarthy Mark I, Melander Olle, Mohlke Karen L, Morris Andrew P, Palmer Colin N A, Pedersen Oluf, Polasek Ozren, Poulter Neil R, Province Michael A, Psaty Bruce M, Ridker Paul M, Rotter Jerome I, Rudan Igor, Salomaa Veikko, Samani Nilesh J, Sever Peter J, Skaaby Tea, Stafford Jeanette M, Starr John M, van der Harst Pim, van der Meer Peter, van Duijn Cornelia M, Vergnaud Anne-Claire, Gudnason Vilmundur, Wareham Nicholas J, Wilson James G, Willer Cristen J, Witte Daniel R, Zeggini Eleftheria, Saleheen Danish, Butterworth Adam S, Danesh John, Asselbergs Folkert W, Wain Louise V, Ehret Georg B, Chasman Daniel I, Caulfield Mark J, Elliott Paul, Lindgren Cecilia M, Levy Daniel, Newton-Cheh Christopher, Munroe Patricia B, Howson Joanna M M
Circ Cardiovasc Genet. 2017 Oct;10(5). doi: 10.1161/CIRCGENETICS.117.001778.
Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.
Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (<5×10) for BP, of which 4 are new BP loci: rs9678851 (missense, ), rs7437940 (), rs13303 (missense, ), and rs1055144 (). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, ) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at ) was genome-wide significant.
We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
全基因组关联研究最近已鉴定出>400个含有影响血压（BP）的DNA序列变异的基因座。我们早期的研究从外显子芯片基因型数据的荟萃分析中鉴定并验证了56个与血压相关的单核苷酸变异（SNV）。另外100个变异产生了关联的提示性证据。
在此，我们纳入了来自英国生物银行的140886名欧洲个体以扩大样本量，其中100个提示性SNV中的77个可用于与收缩压、舒张压或脉压进行关联分析。我们进行了两项荟萃分析，一项针对欧洲、南亚、非洲和西班牙裔血统的个体（泛血统，约475000人），另一项针对欧洲血统个体的子集（约423000人）。21个SNV在全基因组水平上对血压具有显著意义（<5×10），其中4个是新的血压基因座：rs9678851（错义突变， ）、rs7437940（ ）、rs13303（错义突变， ）和rs1055144（ ）。此外，我们在一个已知基因座上鉴定出一个潜在独立的新型血压相关SNV，rs3416322（错义突变， ），它与先前报道的SNV不相关。两个SNV与附近基因的表达水平相关，3个基因座上的SNV与其他性状相关。一个次要等位基因频率<0.01的SNV（ 处的rs3025380）在全基因组水平上具有显著意义。
我们报告了4个与血压调节相关的新基因座，以及一个既定血压基因座上的1个独立变异。该分析突出了几个具有变异的候选基因，这些变异改变了蛋白质功能或基因表达，可供后续研究。
