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

The Understanding Society Scientific Group, behalf of the CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere001778
JournalCirculation: Cardiovascular Genetics
Volume10
Issue number5
DOIs
StatePublished - Oct 1 2017

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Meta-Analysis
Blood Pressure
Nucleotides
Genome
Exome
Genome-Wide Association Study
Hispanic Americans
Gene Frequency
Genes
Genotype
Gene Expression

Keywords

  • blood pressure
  • exome
  • genetics
  • genotype
  • sample size

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

The Understanding Society Scientific Group, & behalf of the CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group (2017). New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals. Circulation: Cardiovascular Genetics, 10(5), [e001778]. https://doi.org/10.1161/CIRCGENETICS.117.001778

New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals. / The Understanding Society Scientific Group; behalf of the CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group.

In: Circulation: Cardiovascular Genetics, Vol. 10, No. 5, e001778, 01.10.2017.

Research output: Contribution to journalArticle

The Understanding Society Scientific Group & behalf of the CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group 2017, 'New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals', Circulation: Cardiovascular Genetics, vol. 10, no. 5, e001778. https://doi.org/10.1161/CIRCGENETICS.117.001778
The Understanding Society Scientific Group, behalf of the CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group. New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals. Circulation: Cardiovascular Genetics. 2017 Oct 1;10(5). e001778. https://doi.org/10.1161/CIRCGENETICS.117.001778
The Understanding Society Scientific Group ; behalf of the CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group. / New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals. In: Circulation: Cardiovascular Genetics. 2017 ; Vol. 10, No. 5.
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abstract = "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.",
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TY - JOUR

T1 - New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals

AU - The Understanding Society Scientific Group

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 - 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 - Ehret, Georg B.

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

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DO - 10.1161/CIRCGENETICS.117.001778

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