TY - JOUR
T1 - New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals
AU - behalf of the CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group
AU - The Understanding Society Scientific Group
AU - Kraja, Aldi T.
AU - Cook, James P.
AU - Warren, Helen R.
AU - Surendran, Praveen
AU - Liu, Chunyu
AU - Evangelou, Evangelos
AU - Manning, Alisa K.
AU - Grarup, Niels
AU - Drenos, Fotios
AU - Sim, Xueling
AU - Smith, Albert Vernon
AU - Amin, Najaf
AU - Blakemore, Alexandra I.F.
AU - Bork-Jensen, Jette
AU - Brandslund, Ivan
AU - Farmaki, Aliki Eleni
AU - Fava, Cristiano
AU - Ferreira, Teresa
AU - Herzig, Karl Heinz
AU - Giri, Ayush
AU - Giulianini, Franco
AU - Grove, Megan L.
AU - Guo, Xiuqing
AU - Harris, Sarah E.
AU - Have, Christian T.
AU - Havulinna, Aki S.
AU - Zhang, He
AU - Jørgensen, Marit E.
AU - Käräjämäki, Anne Mari
AU - Kooperberg, Charles
AU - Linneberg, Allan
AU - Little, Louis
AU - Liu, Yongmei
AU - Bonnycastle, Lori L.
AU - Lu, Yingchang
AU - Mägi, Reedik
AU - Mahajan, Anubha
AU - Malerba, Giovanni
AU - Marioni, Riccardo E.
AU - Mei, Hao
AU - Menni, Cristina
AU - Morrison, Alanna C.
AU - Padmanabhan, Sandosh
AU - Palmas, Walter
AU - Poveda, Alaitz
AU - Rauramaa, Rainer
AU - Rayner, Nigel William
AU - Riaz, Muhammad
AU - Rice, Ken
AU - Province, Michael A.
N1 - Publisher Copyright:
© 2017 American Heart Association, Inc.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - blood pressure
KW - exome
KW - genetics
KW - genotype
KW - sample size
UR - http://www.scopus.com/inward/record.url?scp=85032923056&partnerID=8YFLogxK
U2 - 10.1161/CIRCGENETICS.117.001778
DO - 10.1161/CIRCGENETICS.117.001778
M3 - Article
C2 - 29030403
AN - SCOPUS:85032923056
SN - 1942-325X
VL - 10
JO - Circulation: Cardiovascular Genetics
JF - Circulation: Cardiovascular Genetics
IS - 5
M1 - e001778
ER -