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Discovery of novel heart rate-associated loci using the Exome Chip. / van den Berg, Marten E; Warren, Helen R; Cabrera, Claudia P; Verweij, Niek; Mifsud, Borbala; Haessler, Jeffrey; Bihlmeyer, Nathan A; Fu, Yi-Ping; Weiss, Stefan; Lin, Henry J; Grarup, Niels; Li-Gao, Ruifang; Pistis, Giorgio; Shah, Nabi; Brody, Jennifer A; Müller-Nurasyid, Martina; Lin, Honghuang; Mei, Hao; Smith, Albert V; Lyytikäinen, Leo-Pekka; Hall, Leanne M; van Setten, Jessica; Trompet, Stella; Prins, Bram P; Isaacs, Aaron; Radmanesh, Farid; Marten, Jonathan; Entwistle, Aiman; Kors, Jan A; Silva, Claudia T; Alonso, Alvaro; Bis, Joshua C; de Boer, Rudolf A; de Haan, Hugoline G; de Mutsert, Renée; Dedoussis, George; Dominiczak, Anna F; Doney, Alex S F; Ellinor, Patrick T; Eppinga, Ruben N; Felix, Stephan B; Guo, Xiuqing; Hagemeijer, Yanick; Hansen, Torben; Harris, Tamara B; Heckbert, Susan R; Huang, Paul L; Hwang, Shih-Jen; Kähönen, Mika; Kanters, Jørgen K; Kolcic, Ivana; Launer, Lenore J; Li, Man; Yao, Xiao Jie; Linneberg, Allan; Liu, Simin; Macfarlane, Peter W; Mangino, Massimo; Morris, Andrew D; Mulas, Antonella; Murray, Alison D; Nelson, Christopher P; Orrù, Marco; Padmanabhan, Sandosh; Peters, Annette; Porteous, David J; Poulter, Neil; Psaty, Bruce M; Qi, Lihong; Raitakari, Olli T; Rivadeneira, Fernando; Roselli, Carolina; Rudan, Igor; Sattar, Naveed; Sever, Peter; Sinner, Moritz F; Soliman, Elsayed Z; Spector, Timothy D.; Stanton, Alice V; Stirrups, Kathleen E; Taylor, Kent D; Tobin, Martin D; Uitterlinden, Andre; Vaartjes, Ilonca; Hoes, Arno W; van der Meer, Peter; Völker, Uwe; Waldenberger, Melanie; Xie, Zhijun; Zoledziewska, Magdalena; Tinker, Andrew; Polasek, Ozren; Rosand, Jonathan; Jamshidi, Yalda; van Duijn, Cornélia M; Zeggini, Eleftheria; Jukema, J Wouter; Asselbergs, Folkert W; Samani, Nilesh J; Lehtimäki, Terho; Gudnason, Vilmundur; Wilson, James; Lubitz, Steven A; Kääb, Stefan; Sotoodehnia, Nona; Caulfield, Mark J; Palmer, Colin N A; Sanna, Serena; Mook-Kanamori, Dennis O; Deloukas, Panos; Pedersen, Oluf; Rotter, Jerome I; Dörr, Marcus; O'Donnell, Chris J; Hayward, Caroline; Arking, Dan E; Kooperberg, Charles; van der Harst, Pim; Eijgelsheim, Mark; Stricker, Bruno H Ch; Munroe, Patricia B.
I:
Human Molecular Genetics, Bind 26, Nr. 12, 15.06.2017, s. 2346-2363.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
van den Berg, ME, Warren, HR, Cabrera, CP, Verweij, N, Mifsud, B, Haessler, J, Bihlmeyer, NA, Fu, Y-P, Weiss, S, Lin, HJ
, Grarup, N, Li-Gao, R, Pistis, G, Shah, N, Brody, JA, Müller-Nurasyid, M, Lin, H, Mei, H, Smith, AV, Lyytikäinen, L-P, Hall, LM, van Setten, J, Trompet, S, Prins, BP, Isaacs, A, Radmanesh, F, Marten, J, Entwistle, A, Kors, JA, Silva, CT, Alonso, A, Bis, JC, de Boer, RA, de Haan, HG, de Mutsert, R, Dedoussis, G, Dominiczak, AF, Doney, ASF, Ellinor, PT, Eppinga, RN, Felix, SB, Guo, X, Hagemeijer, Y
, Hansen, T, Harris, TB, Heckbert, SR, Huang, PL, Hwang, S-J, Kähönen, M
, Kanters, JK, Kolcic, I, Launer, LJ, Li, M, Yao, XJ
, Linneberg, A, Liu, S, Macfarlane, PW, Mangino, M, Morris, AD, Mulas, A, Murray, AD, Nelson, CP, Orrù, M, Padmanabhan, S, Peters, A, Porteous, DJ, Poulter, N, Psaty, BM, Qi, L, Raitakari, OT, Rivadeneira, F, Roselli, C, Rudan, I, Sattar, N, Sever, P, Sinner, MF, Soliman, EZ, Spector, TD, Stanton, AV, Stirrups, KE, Taylor, KD, Tobin, MD, Uitterlinden, A, Vaartjes, I, Hoes, AW, van der Meer, P, Völker, U, Waldenberger, M, Xie, Z, Zoledziewska, M, Tinker, A, Polasek, O, Rosand, J, Jamshidi, Y, van Duijn, CM, Zeggini, E, Jukema, JW, Asselbergs, FW, Samani, NJ, Lehtimäki, T, Gudnason, V, Wilson, J, Lubitz, SA, Kääb, S, Sotoodehnia, N, Caulfield, MJ, Palmer, CNA, Sanna, S, Mook-Kanamori, DO, Deloukas, P
, Pedersen, O, Rotter, JI, Dörr, M, O'Donnell, CJ, Hayward, C, Arking, DE, Kooperberg, C, van der Harst, P, Eijgelsheim, M, Stricker, BHC & Munroe, PB 2017, '
Discovery of novel heart rate-associated loci using the Exome Chip',
Human Molecular Genetics, bind 26, nr. 12, s. 2346-2363.
https://doi.org/10.1093/hmg/ddx113APA
van den Berg, M. E., Warren, H. R., Cabrera, C. P., Verweij, N., Mifsud, B., Haessler, J., Bihlmeyer, N. A., Fu, Y-P., Weiss, S., Lin, H. J.
, Grarup, N., Li-Gao, R., Pistis, G., Shah, N., Brody, J. A., Müller-Nurasyid, M., Lin, H., Mei, H., Smith, A. V., ... Munroe, P. B. (2017).
Discovery of novel heart rate-associated loci using the Exome Chip.
Human Molecular Genetics,
26(12), 2346-2363.
https://doi.org/10.1093/hmg/ddx113Vancouver
van den Berg ME, Warren HR, Cabrera CP, Verweij N, Mifsud B, Haessler J o.a.
Discovery of novel heart rate-associated loci using the Exome Chip.
Human Molecular Genetics. 2017 jun. 15;26(12):2346-2363.
https://doi.org/10.1093/hmg/ddx113Author
van den Berg, Marten E ; Warren, Helen R ; Cabrera, Claudia P ; Verweij, Niek ; Mifsud, Borbala ; Haessler, Jeffrey ; Bihlmeyer, Nathan A ; Fu, Yi-Ping ; Weiss, Stefan ; Lin, Henry J ; Grarup, Niels ; Li-Gao, Ruifang ; Pistis, Giorgio ; Shah, Nabi ; Brody, Jennifer A ; Müller-Nurasyid, Martina ; Lin, Honghuang ; Mei, Hao ; Smith, Albert V ; Lyytikäinen, Leo-Pekka ; Hall, Leanne M ; van Setten, Jessica ; Trompet, Stella ; Prins, Bram P ; Isaacs, Aaron ; Radmanesh, Farid ; Marten, Jonathan ; Entwistle, Aiman ; Kors, Jan A ; Silva, Claudia T ; Alonso, Alvaro ; Bis, Joshua C ; de Boer, Rudolf A ; de Haan, Hugoline G ; de Mutsert, Renée ; Dedoussis, George ; Dominiczak, Anna F ; Doney, Alex S F ; Ellinor, Patrick T ; Eppinga, Ruben N ; Felix, Stephan B ; Guo, Xiuqing ; Hagemeijer, Yanick ; Hansen, Torben ; Harris, Tamara B ; Heckbert, Susan R ; Huang, Paul L ; Hwang, Shih-Jen ; Kähönen, Mika ; Kanters, Jørgen K ; Kolcic, Ivana ; Launer, Lenore J ; Li, Man ; Yao, Xiao Jie ; Linneberg, Allan ; Liu, Simin ; Macfarlane, Peter W ; Mangino, Massimo ; Morris, Andrew D ; Mulas, Antonella ; Murray, Alison D ; Nelson, Christopher P ; Orrù, Marco ; Padmanabhan, Sandosh ; Peters, Annette ; Porteous, David J ; Poulter, Neil ; Psaty, Bruce M ; Qi, Lihong ; Raitakari, Olli T ; Rivadeneira, Fernando ; Roselli, Carolina ; Rudan, Igor ; Sattar, Naveed ; Sever, Peter ; Sinner, Moritz F ; Soliman, Elsayed Z ; Spector, Timothy D. ; Stanton, Alice V ; Stirrups, Kathleen E ; Taylor, Kent D ; Tobin, Martin D ; Uitterlinden, Andre ; Vaartjes, Ilonca ; Hoes, Arno W ; van der Meer, Peter ; Völker, Uwe ; Waldenberger, Melanie ; Xie, Zhijun ; Zoledziewska, Magdalena ; Tinker, Andrew ; Polasek, Ozren ; Rosand, Jonathan ; Jamshidi, Yalda ; van Duijn, Cornélia M ; Zeggini, Eleftheria ; Jukema, J Wouter ; Asselbergs, Folkert W ; Samani, Nilesh J ; Lehtimäki, Terho ; Gudnason, Vilmundur ; Wilson, James ; Lubitz, Steven A ; Kääb, Stefan ; Sotoodehnia, Nona ; Caulfield, Mark J ; Palmer, Colin N A ; Sanna, Serena ; Mook-Kanamori, Dennis O ; Deloukas, Panos ; Pedersen, Oluf ; Rotter, Jerome I ; Dörr, Marcus ; O'Donnell, Chris J ; Hayward, Caroline ; Arking, Dan E ; Kooperberg, Charles ; van der Harst, Pim ; Eijgelsheim, Mark ; Stricker, Bruno H Ch ; Munroe, Patricia B. / Discovery of novel heart rate-associated loci using the Exome Chip. I: Human Molecular Genetics. 2017 ; Bind 26, Nr. 12. s. 2346-2363.
Bibtex
@article{3abbe3441e9f4cb4902a406a9ae13065,
title = "Discovery of novel heart rate-associated loci using the Exome Chip",
abstract = "Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.",
keywords = "Journal Article",
author = "{van den Berg}, {Marten E} and Warren, {Helen R} and Cabrera, {Claudia P} and Niek Verweij and Borbala Mifsud and Jeffrey Haessler and Bihlmeyer, {Nathan A} and Yi-Ping Fu and Stefan Weiss and Lin, {Henry J} and Niels Grarup and Ruifang Li-Gao and Giorgio Pistis and Nabi Shah and Brody, {Jennifer A} and Martina M{\"u}ller-Nurasyid and Honghuang Lin and Hao Mei and Smith, {Albert V} and Leo-Pekka Lyytik{\"a}inen and Hall, {Leanne M} and {van Setten}, Jessica and Stella Trompet and Prins, {Bram P} and Aaron Isaacs and Farid Radmanesh and Jonathan Marten and Aiman Entwistle and Kors, {Jan A} and Silva, {Claudia T} and Alvaro Alonso and Bis, {Joshua C} and {de Boer}, {Rudolf A} and {de Haan}, {Hugoline G} and {de Mutsert}, Ren{\'e}e and George Dedoussis and Dominiczak, {Anna F} and Doney, {Alex S F} and Ellinor, {Patrick T} and Eppinga, {Ruben N} and Felix, {Stephan B} and Xiuqing Guo and Yanick Hagemeijer and Torben Hansen and Harris, {Tamara B} and Heckbert, {Susan R} and Huang, {Paul L} and Shih-Jen Hwang and Mika K{\"a}h{\"o}nen and Kanters, {J{\o}rgen K} and Ivana Kolcic and Launer, {Lenore J} and Man Li and Yao, {Xiao Jie} and Allan Linneberg and Simin Liu and Macfarlane, {Peter W} and Massimo Mangino and Morris, {Andrew D} and Antonella Mulas and Murray, {Alison D} and Nelson, {Christopher P} and Marco Orr{\`u} and Sandosh Padmanabhan and Annette Peters and Porteous, {David J} and Neil Poulter and Psaty, {Bruce M} and Lihong Qi and Raitakari, {Olli T} and Fernando Rivadeneira and Carolina Roselli and Igor Rudan and Naveed Sattar and Peter Sever and Sinner, {Moritz F} and Soliman, {Elsayed Z} and Spector, {Timothy D.} and Stanton, {Alice V} and Stirrups, {Kathleen E} and Taylor, {Kent D} and Tobin, {Martin D} and Andre Uitterlinden and Ilonca Vaartjes and Hoes, {Arno W} and {van der Meer}, Peter and Uwe V{\"o}lker and Melanie Waldenberger and Zhijun Xie and Magdalena Zoledziewska and Andrew Tinker and Ozren Polasek and Jonathan Rosand and Yalda Jamshidi and {van Duijn}, {Corn{\'e}lia M} and Eleftheria Zeggini and Jukema, {J Wouter} and Asselbergs, {Folkert W} and Samani, {Nilesh J} and Terho Lehtim{\"a}ki and Vilmundur Gudnason and James Wilson and Lubitz, {Steven A} and Stefan K{\"a}{\"a}b and Nona Sotoodehnia and Caulfield, {Mark J} and Palmer, {Colin N A} and Serena Sanna and Mook-Kanamori, {Dennis O} and Panos Deloukas and Oluf Pedersen and Rotter, {Jerome I} and Marcus D{\"o}rr and O'Donnell, {Chris J} and Caroline Hayward and Arking, {Dan E} and Charles Kooperberg and {van der Harst}, Pim and Mark Eijgelsheim and Stricker, {Bruno H Ch} and Munroe, {Patricia B}",
note = "{\textcopyright} The Author 2017. Published by Oxford University Press.",
year = "2017",
month = jun,
day = "15",
doi = "10.1093/hmg/ddx113",
language = "English",
volume = "26",
pages = "2346--2363",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "12",
}
RIS
TY - JOUR
T1 - Discovery of novel heart rate-associated loci using the Exome Chip
AU - van den Berg, Marten E
AU - Warren, Helen R
AU - Cabrera, Claudia P
AU - Verweij, Niek
AU - Mifsud, Borbala
AU - Haessler, Jeffrey
AU - Bihlmeyer, Nathan A
AU - Fu, Yi-Ping
AU - Weiss, Stefan
AU - Lin, Henry J
AU - Grarup, Niels
AU - Li-Gao, Ruifang
AU - Pistis, Giorgio
AU - Shah, Nabi
AU - Brody, Jennifer A
AU - Müller-Nurasyid, Martina
AU - Lin, Honghuang
AU - Mei, Hao
AU - Smith, Albert V
AU - Lyytikäinen, Leo-Pekka
AU - Hall, Leanne M
AU - van Setten, Jessica
AU - Trompet, Stella
AU - Prins, Bram P
AU - Isaacs, Aaron
AU - Radmanesh, Farid
AU - Marten, Jonathan
AU - Entwistle, Aiman
AU - Kors, Jan A
AU - Silva, Claudia T
AU - Alonso, Alvaro
AU - Bis, Joshua C
AU - de Boer, Rudolf A
AU - de Haan, Hugoline G
AU - de Mutsert, Renée
AU - Dedoussis, George
AU - Dominiczak, Anna F
AU - Doney, Alex S F
AU - Ellinor, Patrick T
AU - Eppinga, Ruben N
AU - Felix, Stephan B
AU - Guo, Xiuqing
AU - Hagemeijer, Yanick
AU - Hansen, Torben
AU - Harris, Tamara B
AU - Heckbert, Susan R
AU - Huang, Paul L
AU - Hwang, Shih-Jen
AU - Kähönen, Mika
AU - Kanters, Jørgen K
AU - Kolcic, Ivana
AU - Launer, Lenore J
AU - Li, Man
AU - Yao, Xiao Jie
AU - Linneberg, Allan
AU - Liu, Simin
AU - Macfarlane, Peter W
AU - Mangino, Massimo
AU - Morris, Andrew D
AU - Mulas, Antonella
AU - Murray, Alison D
AU - Nelson, Christopher P
AU - Orrù, Marco
AU - Padmanabhan, Sandosh
AU - Peters, Annette
AU - Porteous, David J
AU - Poulter, Neil
AU - Psaty, Bruce M
AU - Qi, Lihong
AU - Raitakari, Olli T
AU - Rivadeneira, Fernando
AU - Roselli, Carolina
AU - Rudan, Igor
AU - Sattar, Naveed
AU - Sever, Peter
AU - Sinner, Moritz F
AU - Soliman, Elsayed Z
AU - Spector, Timothy D.
AU - Stanton, Alice V
AU - Stirrups, Kathleen E
AU - Taylor, Kent D
AU - Tobin, Martin D
AU - Uitterlinden, Andre
AU - Vaartjes, Ilonca
AU - Hoes, Arno W
AU - van der Meer, Peter
AU - Völker, Uwe
AU - Waldenberger, Melanie
AU - Xie, Zhijun
AU - Zoledziewska, Magdalena
AU - Tinker, Andrew
AU - Polasek, Ozren
AU - Rosand, Jonathan
AU - Jamshidi, Yalda
AU - van Duijn, Cornélia M
AU - Zeggini, Eleftheria
AU - Jukema, J Wouter
AU - Asselbergs, Folkert W
AU - Samani, Nilesh J
AU - Lehtimäki, Terho
AU - Gudnason, Vilmundur
AU - Wilson, James
AU - Lubitz, Steven A
AU - Kääb, Stefan
AU - Sotoodehnia, Nona
AU - Caulfield, Mark J
AU - Palmer, Colin N A
AU - Sanna, Serena
AU - Mook-Kanamori, Dennis O
AU - Deloukas, Panos
AU - Pedersen, Oluf
AU - Rotter, Jerome I
AU - Dörr, Marcus
AU - O'Donnell, Chris J
AU - Hayward, Caroline
AU - Arking, Dan E
AU - Kooperberg, Charles
AU - van der Harst, Pim
AU - Eijgelsheim, Mark
AU - Stricker, Bruno H Ch
AU - Munroe, Patricia B
N1 - © The Author 2017. Published by Oxford University Press.
PY - 2017/6/15
Y1 - 2017/6/15
N2 - Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.
AB - Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.
KW - Journal Article
U2 - 10.1093/hmg/ddx113
DO - 10.1093/hmg/ddx113
M3 - Journal article
C2 - 28379579
VL - 26
SP - 2346
EP - 2363
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 12
ER -
