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

CHD Exome+ Consortium, ExomeBP Consortium, GoT2D Genes Consortium, The UK Biobank CardioMetabolic Consortium BP working group, 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 FarmakiCristiano 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, Anne Mari 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, John M Connell, Andrew P. Morris, Colin N.A. Palmer, Understanding Society Scientific Group, CHARGE EXOME BP

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)
454 Downloads (Pure)


Background: Genome-wide association studies have recently identified over 400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier work 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 or diastolic blood pressure (SBP, DBP) or pulse pressure (PP). We performed two metaanalyses, one in individuals of European, South Asian, African and Hispanic descent (panancestry, ~475,000), and the other in the subset of individuals of European descent (~423,000). Twenty-one SNVs were genome-wide significant (P < 5x10-8) for BP, of which four 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 three 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 four novel loci associated with BP regulation, and one 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.
Original languageEnglish
Article numbere001778
JournalCirculation: Cardiovascular Genetics
Issue number5
Publication statusPublished - 13 Oct 2017


  • Blood Pressure
  • Genetics
  • Genetic, Association Studies
  • Gene Expression and Regulation
  • Exome chip
  • UK Biobank


Dive into the research topics of 'New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals'. Together they form a unique fingerprint.

Cite this