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

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 & 31 andre 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, Cramer K Christensen, Torben Hansen, Understanding Society Scientific Group

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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.

OriginalsprogEngelsk
Artikelnummere001778
TidsskriftCirculation: Cardiovascular Genetics
Vol/bind10
Udgave nummer5
ISSN1942-325X
DOI
StatusUdgivet - 2017

Fingeraftryk

Meta-Analysis
Exome
Genome-Wide Association Study

Citer dette

Kraja, A. T., Cook, J. P., Warren, H. R., Surendran, P., Liu, C., Evangelou, E., ... Understanding Society Scientific 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
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 ; Christensen, Cramer K ; Hansen, Torben ; Understanding Society Scientific Group. / New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals. I: Circulation: Cardiovascular Genetics. 2017 ; Bind 10, Nr. 5.
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title = "New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals",
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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author = "Kraja, {Aldi T} and Cook, {James P} and Warren, {Helen R} and Praveen Surendran and Chunyu Liu and Evangelos Evangelou and Manning, {Alisa K} and Niels Grarup and Fotios Drenos and Xueling Sim and Smith, {Albert Vernon} and Najaf Amin and Blakemore, {Alexandra I F} and Jette Bork-Jensen and Ivan Brandslund and Aliki-Eleni Farmaki and Cristiano Fava and Teresa Ferreira and Karl-Heinz Herzig and Ayush Giri and Franco Giulianini and Grove, {Megan L} and Xiuqing Guo and Harris, {Sarah E} and Have, {Christian T} and Havulinna, {Aki S} and He Zhang and J{\o}rgensen, {Marit E} and AnneMari K{\"a}r{\"a}j{\"a}m{\"a}ki and Charles Kooperberg and Allan Linneberg and Louis Little and Yongmei Liu and Bonnycastle, {Lori L} and Yingchang Lu and Reedik M{\"a}gi and Anubha Mahajan and Giovanni Malerba and Marioni, {Riccardo E} and Hao Mei and Cristina Menni and Morrison, {Alanna C} and Sandosh Padmanabhan and Walter Palmas and Alaitz Poveda and Rainer Rauramaa and Rayner, {Nigel William} and Muhammad Riaz and Christensen, {Cramer K} and Torben Hansen and {Understanding Society Scientific Group}",
note = "{\circledC} 2017 American Heart Association, Inc.",
year = "2017",
doi = "10.1161/CIRCGENETICS.117.001778",
language = "English",
volume = "10",
journal = "Circulation: Cardiovascular Genetics",
issn = "1942-325X",
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Kraja, AT, Cook, JP, Warren, HR, Surendran, P, Liu, C, Evangelou, E, Manning, AK, Grarup, N, Drenos, F, Sim, X, Smith, AV, Amin, N, Blakemore, AIF, Bork-Jensen, J, Brandslund, I, Farmaki, A-E, Fava, C, Ferreira, T, Herzig, K-H, Giri, A, Giulianini, F, Grove, ML, Guo, X, Harris, SE, Have, CT, Havulinna, AS, Zhang, H, Jørgensen, ME, Käräjämäki, A, Kooperberg, C, Linneberg, A, Little, L, Liu, Y, Bonnycastle, LL, Lu, Y, Mägi, R, Mahajan, A, Malerba, G, Marioni, RE, Mei, H, Menni, C, Morrison, AC, Padmanabhan, S, Palmas, W, Poveda, A, Rauramaa, R, Rayner, NW, Riaz, M, Christensen, CK, Hansen, T & Understanding Society Scientific Group 2017, 'New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals', Circulation: Cardiovascular Genetics, bind 10, nr. 5, e001778. https://doi.org/10.1161/CIRCGENETICS.117.001778

New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals. / 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; Christensen, Cramer K; Hansen, Torben; Understanding Society Scientific Group.

I: Circulation: Cardiovascular Genetics, Bind 10, Nr. 5, e001778, 2017.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

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

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, AnneMari

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 - Christensen, Cramer K

AU - Hansen, Torben

AU - Understanding Society Scientific Group

N1 - © 2017 American Heart Association, Inc.

PY - 2017

Y1 - 2017

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 - Journal Article

U2 - 10.1161/CIRCGENETICS.117.001778

DO - 10.1161/CIRCGENETICS.117.001778

M3 - Journal article

VL - 10

JO - Circulation: Cardiovascular Genetics

JF - Circulation: Cardiovascular Genetics

SN - 1942-325X

IS - 5

M1 - e001778

ER -