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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals. / Surendran, Praveen; Feofanova, Elena V.; Lahrouchi, Najim; Ntalla, Ioanna; Karthikeyan, Savita; Cook, James; Chen, Lingyan; Mifsud, Borbala; Yao, Chen; Kraja, Aldi T.; Cartwright, James H.; Hellwege, Jacklyn N.; Giri, Ayush; Tragante, Vinicius; Thorleifsson, Gudmar; Liu, Dajiang J.; Prins, Bram P.; Stewart, Isobel D.; Cabrera, Claudia P.; Eales, James M.; Akbarov, Artur; Auer, Paul L.; Bielak, Lawrence F.; Bis, Joshua C.; Braithwaite, Vickie S.; Brody, Jennifer A.; Daw, E. Warwick; Warren, Helen R.; Drenos, Fotios; Nielsen, Sune Fallgaard; Faul, Jessica D.; Fauman, Eric B.; Fava, Cristiano; Varga, Tibor V.; Zhao, Jing Hua; Bork-Jensen, Jette; Grarup, Niels; Hansen, Torben; Have, Christian T.; Jørgensen, Marit E.; Karpe, Fredrik; Linneberg, Allan; Pedersen, Oluf; Rasmussen, Katrine L.; Sun, Yan V.; Witte, Daniel R.; Lind, Lars; Loos, Ruth J.F.; Nordestgaard, Børge Grønne; LifeLines Cohort Study; EPIC-CVD; EPIC-InterAct; Understanding Society Scientific Group; Million Veteran Program.
In:
Nature Genetics, Vol. 52, No. 12, 2020, p. 1314-1332.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Surendran, P, Feofanova, EV, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Varga, TV, Zhao, JH, Bork-Jensen, J
, Grarup, N, Hansen, T, Have, CT, Jørgensen, ME, Karpe, F
, Linneberg, A, Pedersen, O, Rasmussen, KL, Sun, YV, Witte, DR, Lind, L
, Loos, RJF, Nordestgaard, BG, LifeLines Cohort Study, EPIC-CVD, EPIC-InterAct, Understanding Society Scientific Group & Million Veteran Program 2020, '
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals',
Nature Genetics, vol. 52, no. 12, pp. 1314-1332.
https://doi.org/10.1038/s41588-020-00713-xAPA
Surendran, P., Feofanova, E. V., Lahrouchi, N., Ntalla, I., Karthikeyan, S., Cook, J., Chen, L., Mifsud, B., Yao, C., Kraja, A. T., Cartwright, J. H., Hellwege, J. N., Giri, A., Tragante, V., Thorleifsson, G., Liu, D. J., Prins, B. P., Stewart, I. D., Cabrera, C. P., ... Million Veteran Program (2020).
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.
Nature Genetics,
52(12), 1314-1332.
https://doi.org/10.1038/s41588-020-00713-xVancouver
Surendran P, Feofanova EV, Lahrouchi N, Ntalla I, Karthikeyan S, Cook J et al.
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.
Nature Genetics. 2020;52(12):1314-1332.
https://doi.org/10.1038/s41588-020-00713-xAuthor
Surendran, Praveen ; Feofanova, Elena V. ; Lahrouchi, Najim ; Ntalla, Ioanna ; Karthikeyan, Savita ; Cook, James ; Chen, Lingyan ; Mifsud, Borbala ; Yao, Chen ; Kraja, Aldi T. ; Cartwright, James H. ; Hellwege, Jacklyn N. ; Giri, Ayush ; Tragante, Vinicius ; Thorleifsson, Gudmar ; Liu, Dajiang J. ; Prins, Bram P. ; Stewart, Isobel D. ; Cabrera, Claudia P. ; Eales, James M. ; Akbarov, Artur ; Auer, Paul L. ; Bielak, Lawrence F. ; Bis, Joshua C. ; Braithwaite, Vickie S. ; Brody, Jennifer A. ; Daw, E. Warwick ; Warren, Helen R. ; Drenos, Fotios ; Nielsen, Sune Fallgaard ; Faul, Jessica D. ; Fauman, Eric B. ; Fava, Cristiano ; Varga, Tibor V. ; Zhao, Jing Hua ; Bork-Jensen, Jette ; Grarup, Niels ; Hansen, Torben ; Have, Christian T. ; Jørgensen, Marit E. ; Karpe, Fredrik ; Linneberg, Allan ; Pedersen, Oluf ; Rasmussen, Katrine L. ; Sun, Yan V. ; Witte, Daniel R. ; Lind, Lars ; Loos, Ruth J.F. ; Nordestgaard, Børge Grønne ; LifeLines Cohort Study ; EPIC-CVD ; EPIC-InterAct ; Understanding Society Scientific Group ; Million Veteran Program. / Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals. In: Nature Genetics. 2020 ; Vol. 52, No. 12. pp. 1314-1332.
Bibtex
@article{75a51416012f4f0cab56a0bcb3b3d43a,
title = "Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals",
abstract = "Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.",
author = "Praveen Surendran and Feofanova, {Elena V.} and Najim Lahrouchi and Ioanna Ntalla and Savita Karthikeyan and James Cook and Lingyan Chen and Borbala Mifsud and Chen Yao and Kraja, {Aldi T.} and Cartwright, {James H.} and Hellwege, {Jacklyn N.} and Ayush Giri and Vinicius Tragante and Gudmar Thorleifsson and Liu, {Dajiang J.} and Prins, {Bram P.} and Stewart, {Isobel D.} and Cabrera, {Claudia P.} and Eales, {James M.} and Artur Akbarov and Auer, {Paul L.} and Bielak, {Lawrence F.} and Bis, {Joshua C.} and Braithwaite, {Vickie S.} and Brody, {Jennifer A.} and Daw, {E. Warwick} and Warren, {Helen R.} and Fotios Drenos and Nielsen, {Sune Fallgaard} and Faul, {Jessica D.} and Fauman, {Eric B.} and Cristiano Fava and Varga, {Tibor V.} and Zhao, {Jing Hua} and Jette Bork-Jensen and Niels Grarup and Torben Hansen and Have, {Christian T.} and J{\o}rgensen, {Marit E.} and Fredrik Karpe and Allan Linneberg and Oluf Pedersen and Rasmussen, {Katrine L.} and Sun, {Yan V.} and Witte, {Daniel R.} and Lars Lind and Loos, {Ruth J.F.} and Nordestgaard, {B{\o}rge Gr{\o}nne} and {LifeLines Cohort Study} and EPIC-CVD and EPIC-InterAct and {Understanding Society Scientific Group} and {Million Veteran Program}",
note = "Correction: https://doi.org/10.1038/s41588-021-00832-z",
year = "2020",
doi = "10.1038/s41588-020-00713-x",
language = "English",
volume = "52",
pages = "1314--1332",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "12",
}
RIS
TY - JOUR
T1 - Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
AU - Surendran, Praveen
AU - Feofanova, Elena V.
AU - Lahrouchi, Najim
AU - Ntalla, Ioanna
AU - Karthikeyan, Savita
AU - Cook, James
AU - Chen, Lingyan
AU - Mifsud, Borbala
AU - Yao, Chen
AU - Kraja, Aldi T.
AU - Cartwright, James H.
AU - Hellwege, Jacklyn N.
AU - Giri, Ayush
AU - Tragante, Vinicius
AU - Thorleifsson, Gudmar
AU - Liu, Dajiang J.
AU - Prins, Bram P.
AU - Stewart, Isobel D.
AU - Cabrera, Claudia P.
AU - Eales, James M.
AU - Akbarov, Artur
AU - Auer, Paul L.
AU - Bielak, Lawrence F.
AU - Bis, Joshua C.
AU - Braithwaite, Vickie S.
AU - Brody, Jennifer A.
AU - Daw, E. Warwick
AU - Warren, Helen R.
AU - Drenos, Fotios
AU - Nielsen, Sune Fallgaard
AU - Faul, Jessica D.
AU - Fauman, Eric B.
AU - Fava, Cristiano
AU - Varga, Tibor V.
AU - Zhao, Jing Hua
AU - Bork-Jensen, Jette
AU - Grarup, Niels
AU - Hansen, Torben
AU - Have, Christian T.
AU - Jørgensen, Marit E.
AU - Karpe, Fredrik
AU - Linneberg, Allan
AU - Pedersen, Oluf
AU - Rasmussen, Katrine L.
AU - Sun, Yan V.
AU - Witte, Daniel R.
AU - Lind, Lars
AU - Loos, Ruth J.F.
AU - Nordestgaard, Børge Grønne
AU - LifeLines Cohort Study
AU - EPIC-CVD
AU - EPIC-InterAct
AU - Understanding Society Scientific Group
AU - Million Veteran Program
N1 - Correction: https://doi.org/10.1038/s41588-021-00832-z
PY - 2020
Y1 - 2020
N2 - Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
AB - Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
U2 - 10.1038/s41588-020-00713-x
DO - 10.1038/s41588-020-00713-x
M3 - Journal article
C2 - 33230300
AN - SCOPUS:85096546970
VL - 52
SP - 1314
EP - 1332
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 12
ER -
