New Blood Pressure–Associated Loci Identified in Meta-Analyses of 475 000 Individuals
Authors: 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 ,   The Understanding Society Scientific Group, 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. 
Published: October 2017

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 (
P
<5×10
−
8
) for BP, of which 4 are new BP loci: rs9678851 (missense,
SLC4A1AP
), rs7437940 (
AFAP1
), rs13303 (missense,
STAB1
), and rs1055144 (
7p15.2
). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense,
SYNPO2L
) 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
DBH
) 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.