New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals.

Authors:
Aldi T Kraja James P Cook Helen R Warren Praveen Surendran Chunyu Liu Evangelos Evangelou Alisa K Manning Niels Grarup Fotios Drenos Xueling Sim Albert Vernon Smith Najaf Amin Alexandra I F Blakemore Jette Bork-Jensen Ivan Brandslund Aliki-Eleni Farmaki Cristiano Fava Teresa Ferreira Karl-Heinz Herzig Ayush Giri Franco Giulianini Megan L Grove Xiuqing Guo Sarah E Harris Christian T Have Aki S Havulinna He Zhang Marit E Jørgensen AnneMari Käräjämäki Charles Kooperberg Allan Linneberg Louis Little Yongmei Liu Lori L Bonnycastle Yingchang Lu Reedik Mägi Anubha Mahajan Giovanni Malerba Riccardo E Marioni Hao Mei Cristina Menni Alanna C Morrison Sandosh Padmanabhan Walter Palmas Alaitz Poveda Rainer Rauramaa Nigel William Rayner Muhammad Riaz Ken Rice Melissa A Richard Jennifer A Smith Lorraine Southam Alena Stančáková Kathleen E Stirrups Vinicius Tragante Tiinamaija Tuomi Ioanna Tzoulaki Tibor V Varga Stefan Weiss Andrianos M Yiorkas Robin Young Weihua Zhang Michael R Barnes Claudia P Cabrera He Gao Michael Boehnke Eric Boerwinkle John C Chambers John M Connell Cramer K Christensen Rudolf A de Boer Ian J Deary George Dedoussis Panos Deloukas Anna F Dominiczak Marcus Dörr Roby Joehanes Todd L Edwards Tõnu Esko Myriam Fornage Nora Franceschini Paul W Franks Giovanni Gambaro Leif Groop Göran Hallmans Torben Hansen Caroline Hayward Oksa Heikki Erik Ingelsson Jaakko Tuomilehto Marjo-Riitta Jarvelin Sharon L R Kardia Fredrik Karpe Jaspal S Kooner Timo A Lakka Claudia Langenberg Lars Lind Ruth J F Loos Markku Laakso Mark I McCarthy Olle Melander Karen L Mohlke Andrew P Morris Colin N A Palmer Oluf Pedersen Ozren Polasek Neil R Poulter Michael A Province Bruce M Psaty Paul M Ridker Jerome I Rotter Igor Rudan Veikko Salomaa Nilesh J Samani Peter J Sever Tea Skaaby Jeanette M Stafford John M Starr Pim van der Harst Peter van der Meer Cornelia M van Duijn Anne-Claire Vergnaud Vilmundur Gudnason Nicholas J Wareham James G Wilson Cristen J Willer Daniel R Witte Eleftheria Zeggini Danish Saleheen Adam S Butterworth John Danesh Folkert W Asselbergs Louise V Wain Georg B Ehret Daniel I Chasman Mark J Caulfield Paul Elliott Cecilia M Lindgren Daniel Levy Christopher Newton-Cheh Patricia B Munroe Joanna M M Howson

Circ Cardiovasc Genet 2017 Oct;10(5)

Background: 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.

Methods And Results: 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.

Conclusions: 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.

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http://dx.doi.org/10.1161/CIRCGENETICS.117.001778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776077PMC
October 2017
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