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40 results on '"Krijthe, Bouwe P."'

1. Is methotrexate safe for men with an immune-mediated inflammatory disease and an active desire to become a father? Results of a prospective cohort study (iFAME-MTX)

Author: Perez-Garcia, Luis Fernando, Röder, Esther, Krijthe, Bouwe P., Kranenburg-Van Koppen, Laura J.C., Van Adrichem, Roxanne, Zirkzee, Els, Griffioen, Pieter H., Peeters, Kris, Lin, Marry, Struys, Eduard A., Jansen, Gerrit, Van Doorn, Martijn B.A., De Jonge, Robert, Dohle, Gert R., Dolhain, Radboud J.E.M., Perez-Garcia, Luis Fernando, Röder, Esther, Krijthe, Bouwe P., Kranenburg-Van Koppen, Laura J.C., Van Adrichem, Roxanne, Zirkzee, Els, Griffioen, Pieter H., Peeters, Kris, Lin, Marry, Struys, Eduard A., Jansen, Gerrit, Van Doorn, Martijn B.A., De Jonge, Robert, Dohle, Gert R., and Dolhain, Radboud J.E.M.
Abstract: Introduction Current scientific evidence guiding the decision whether men with an active desire to become a father should be treated with methotrexate (MTX) remains controversial. We aimed to prospectively evaluate the testicular toxicity profile of MTX focusing on several markers of male fertility, including semen parameters and sperm DNA fragmentation index (sDFI). As a secondary outcome, we aimed to evaluate whether MTX-polyglutamates can be detected in spermatozoa and seminal plasma and to evaluate the enzymatic activity in spermatozoa of folylpolyglutamate synthetase (FPGS). Methods In a prospective cohort study, men ≥18 years who started therapy with MTX were invited to participate (MTX-starters). Participants were instructed to produce two semen samples (a pre-exposure and a post-exposure sample after 13 weeks). Healthy men ≥18 years were invited to participate as controls. Conventional semen analyses, male reproductive endocrine axis and sDFI were compared between groups. FPGS enzymatic activity and MTX-PG1-5 concentrations were determined by mass spectrometry analytical methods. Results In total, 20 MTX-starters and 25 controls were included. The pre-exposure and postexposure semen parameters of MTX-starters were not statistically significant different. Compared with healthy controls, the conventional semen parameters and the sDFI of MTX-starters were not statistically significant different. These data were corroborated by the marginal accumulation of MTX-PGs in spermatozoa, consistent with the very low FPGS enzymatic activity associated with the expression of an alternative FPGS splice-variant. Discussion Treatment with MTX is not associated with testicular toxicity, consistent with the very low concentration of intracellular MTX-PG. Therefore, therapy with MTX can be safely started or continued in men and with a wish to become a father.
Published: 2023

2. Paternal inflammatory arthritis is associated with a higher risk of miscarriage:results of a large multicentre study (iFAME-Fertility)

Author: Perez-Garcia, Luis F, Röder, Esther, Smeele, Hieronymus T W, Goekoop, Robbert, Hazes, Johanna M W, Kok, Marc R, Tchetverikov, Ilja, van der Helm-van Mil, Annette, van der Kaap, Jos, Kok, Petra, Krijthe, Bouwe P, Dolhain, Radboud J E M, Perez-Garcia, Luis F, Röder, Esther, Smeele, Hieronymus T W, Goekoop, Robbert, Hazes, Johanna M W, Kok, Marc R, Tchetverikov, Ilja, van der Helm-van Mil, Annette, van der Kaap, Jos, Kok, Petra, Krijthe, Bouwe P, and Dolhain, Radboud J E M
Abstract: Objectives: Paternal preconception health is recognized as an important contributor to pregnancy outcomes. Nonetheless, pregnancy outcomes of partners of men with inflammatory arthritis (IA) have never been studied. Our objective was to describe the pregnancy outcomes of partners of men diagnosed with IA. Methods: We performed a multicentre cross-sectional retrospective study conducted in the Netherlands. Men with IA who were over 40 years old that reported at least one positive pregnancy test were included. To analyse the impact of IA on pregnancy outcomes, pregnancies were classified into two groups: pregnancies conceived after the diagnosis of IA and before the diagnosis of IA. Results: In total, 408 male participants diagnosed with IA reported 897 singleton pregnancies that resulted in 794 live births. Pregnancies conceived after the diagnosis of IA had higher rate of miscarriage (12.27 vs 7.53%, P = <0.05). This increased risk was still present after adjusting for confounders [OR 2.03 (95% CI 1.12, 3.69) P = 0.015]. Conclusions: This is the largest study to describe the pregnancy outcomes of partners of men diagnosed with IA and the first to demonstrate that paternal IA is associated with a higher risk of miscarriage. Notwithstanding, the overall rate of miscarriage reported in our study could be comparable to previously reported population estimates.
Published: 2022

3. Impaired fertility in men diagnosed with inflammatory arthritis:Results of a large multicentre study (iFAME-Fertility)

Author: Perez-Garcia, Luis Fernando, Röder, Esther, Goekoop, Robbert J., Hazes, Johanna M.W., Kok, Marc R., Smeele, Hieronymus T.W., Tchetverikov, Ilja, Van Der Helm-Van Mil, Annette H.M., Van Der Kaap, Jos H., Kok, Petra, Krijthe, Bouwe P., Dolhain, Radboud J.E.M., Perez-Garcia, Luis Fernando, Röder, Esther, Goekoop, Robbert J., Hazes, Johanna M.W., Kok, Marc R., Smeele, Hieronymus T.W., Tchetverikov, Ilja, Van Der Helm-Van Mil, Annette H.M., Van Der Kaap, Jos H., Kok, Petra, Krijthe, Bouwe P., and Dolhain, Radboud J.E.M.
Abstract: Objectives The impact of inflammatory arthritis (IA) on male fertility remains unexplored. Our objective was to evaluate the impact of IA on several male fertility outcomes; fertility rate (number of biological children per man), family planning, childlessness and fertility problems. Methods We performed a multicentre cross-sectional study (iFAME-Fertility). Men with IA 40 years or older who indicated that their family size was complete were invited to participate. Participants completed a questionnaire that included demographic, medical and fertility-related questions. To analyse the impact of IA on fertility rate, patients were divided into groups according to the age at the time of their diagnosis: ≤30 years (before the peak of reproductive age), between 31 and 40 years (during the peak) and ≥41 years (after the peak). Results In total 628 participants diagnosed with IA were included. Men diagnosed ≤30 years had a lower mean number of children (1.32 (SD 1.14)) than men diagnosed between 31 and 40 years (1.60 (SD 1.35)) and men diagnosed ≥41 years (1.88 (SD 1.14)).This was statistically significant (p=0.0004).The percentages of men diagnosed ≤30 and 31-40 years who were involuntary childless (12.03% vs 10.34% vs 3.98%, p=0.001) and who reported having received medical evaluations for fertility problems (20.61%, 20.69% and 11.36%, p=0.027) were statistically significant higher than men diagnosed ≥41 years. Conclusions This is the first study that shows that IA can impair male fertility. Men diagnosed with IA before and during the peak of reproductive age had a lower fertility rate, higher childlessness rate and more fertility problems. Increased awareness and more research into the causes behind this association are urgently needed.
Published: 2021

4. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikainen, Leo-Pekka, Mueller, Christian, Mueller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kahonen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J. F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Aldana, Claudia T. Silva, Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Westra, Harm Jan, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Doerr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kaeaeb, Stefan, Lehtimaki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I. W., Isaacs, Aaron, Arking, Dan E., Sotoodehnia, Nona, van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikainen, Leo-Pekka, Mueller, Christian, Mueller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kahonen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J. F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Aldana, Claudia T. Silva, Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Westra, Harm Jan, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Doerr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kaeaeb, Stefan, Lehtimaki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I. W., Isaacs, Aaron, Arking, Dan E., and Sotoodehnia, Nona
Abstract: Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
Published: 2018
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5. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikainen, Leo-Pekka, Mueller, Christian, Mueller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kahonen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J. F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Aldana, Claudia T. Silva, Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Westra, Harm Jan, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Doerr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kaeaeb, Stefan, Lehtimaki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I. W., Isaacs, Aaron, Arking, Dan E., Sotoodehnia, Nona, van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikainen, Leo-Pekka, Mueller, Christian, Mueller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kahonen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J. F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Aldana, Claudia T. Silva, Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Westra, Harm Jan, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Doerr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kaeaeb, Stefan, Lehtimaki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I. W., Isaacs, Aaron, Arking, Dan E., and Sotoodehnia, Nona
Abstract: Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
Published: 2018
Full Text: View/download PDF

6. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikainen, Leo-Pekka, Mueller, Christian, Mueller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kahonen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J. F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Aldana, Claudia T. Silva, Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Westra, Harm Jan, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Doerr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kaeaeb, Stefan, Lehtimaki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I. W., Isaacs, Aaron, Arking, Dan E., Sotoodehnia, Nona, van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikainen, Leo-Pekka, Mueller, Christian, Mueller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kahonen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J. F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Aldana, Claudia T. Silva, Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Westra, Harm Jan, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Doerr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kaeaeb, Stefan, Lehtimaki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I. W., Isaacs, Aaron, Arking, Dan E., and Sotoodehnia, Nona
Abstract: Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
Published: 2018
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7. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikäinen, Leo Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J.F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Silva Aldana, Claudia T., Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Dörr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kääb, Stefan, Lehtimäki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I.W., Isaacs, Aaron, Arking, Dan E., Sotoodehnia, Nona, van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikäinen, Leo Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J.F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Silva Aldana, Claudia T., Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Dörr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kääb, Stefan, Lehtimäki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I.W., Isaacs, Aaron, Arking, Dan E., and Sotoodehnia, Nona
Published: 2018

8. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikäinen, Leo Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J.F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Silva Aldana, Claudia T., Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Dörr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kääb, Stefan, Lehtimäki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I.W., Isaacs, Aaron, Arking, Dan E., Sotoodehnia, Nona, van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikäinen, Leo Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J.F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Silva Aldana, Claudia T., Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Dörr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kääb, Stefan, Lehtimäki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I.W., Isaacs, Aaron, Arking, Dan E., and Sotoodehnia, Nona
Published: 2018

9. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikäinen, Leo Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J.F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Silva Aldana, Claudia T., Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Dörr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kääb, Stefan, Lehtimäki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I.W., Isaacs, Aaron, Arking, Dan E., Sotoodehnia, Nona, van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikäinen, Leo Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J.F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Silva Aldana, Claudia T., Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Dörr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kääb, Stefan, Lehtimäki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I.W., Isaacs, Aaron, Arking, Dan E., and Sotoodehnia, Nona
Published: 2018

10. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.

Author: van Setten, Jessica, van Setten, Jessica, Brody, Jennifer A, Jamshidi, Yalda, Swenson, Brenton R, Butler, Anne M, Campbell, Harry, Del Greco, Fabiola M, Evans, Daniel S, Gibson, Quince, Gudbjartsson, Daniel F, Kerr, Kathleen F, Krijthe, Bouwe P, Lyytikäinen, Leo-Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M, Padmanabhan, Sandosh, Ritchie, Marylyn D, Robino, Antonietta, Smith, Albert V, Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O, Asselbergs, Folkert W, Bader, Joel S, Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M, Chung, Mina K, Crawford, Dana, den Hoed, Marcel, Denny, Josh C, Dominiczak, Anna F, Ehret, Georg B, Eijgelsheim, Mark, Ellinor, Patrick T, Felix, Stephan B, Franco, Oscar H, Franke, Lude, Harris, Tamara B, Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A, Lakatta, Edward G, Launer, Lenore J, Lin, Honghuang, Lin, Henry J, Loos, Ruth JF, Lubitz, Steven A, Macfarlane, Peter W, Magnani, Jared W, Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D, Munzel, Thomas, Papanicolaou, George J, Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P, Raitakari, Olli T, Rotter, Jerome I, Rudan, Igor, Samani, Nilesh J, Schlessinger, David, Silva Aldana, Claudia T, Sinner, Moritz F, Smith, Jonathan D, Snieder, Harold, Soliman, Elsayed Z, Spector, Timothy D, Stott, David J, Strauch, Konstantin, Tarasov, Kirill V, Thorsteinsdottir, Unnur, Uitterlinden, Andre G, Van Wagoner, David R, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S, Zeller, Tanja, Alonso, Alvaro, Avery, Christy L, Bandinelli, Stefania, Benjamin, Emelia J, Cucca, Francesco, Dörr, Marcus, Ferrucci, Luigi, van Setten, Jessica, van Setten, Jessica, Brody, Jennifer A, Jamshidi, Yalda, Swenson, Brenton R, Butler, Anne M, Campbell, Harry, Del Greco, Fabiola M, Evans, Daniel S, Gibson, Quince, Gudbjartsson, Daniel F, Kerr, Kathleen F, Krijthe, Bouwe P, Lyytikäinen, Leo-Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M, Padmanabhan, Sandosh, Ritchie, Marylyn D, Robino, Antonietta, Smith, Albert V, Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O, Asselbergs, Folkert W, Bader, Joel S, Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M, Chung, Mina K, Crawford, Dana, den Hoed, Marcel, Denny, Josh C, Dominiczak, Anna F, Ehret, Georg B, Eijgelsheim, Mark, Ellinor, Patrick T, Felix, Stephan B, Franco, Oscar H, Franke, Lude, Harris, Tamara B, Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A, Lakatta, Edward G, Launer, Lenore J, Lin, Honghuang, Lin, Henry J, Loos, Ruth JF, Lubitz, Steven A, Macfarlane, Peter W, Magnani, Jared W, Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D, Munzel, Thomas, Papanicolaou, George J, Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P, Raitakari, Olli T, Rotter, Jerome I, Rudan, Igor, Samani, Nilesh J, Schlessinger, David, Silva Aldana, Claudia T, Sinner, Moritz F, Smith, Jonathan D, Snieder, Harold, Soliman, Elsayed Z, Spector, Timothy D, Stott, David J, Strauch, Konstantin, Tarasov, Kirill V, Thorsteinsdottir, Unnur, Uitterlinden, Andre G, Van Wagoner, David R, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S, Zeller, Tanja, Alonso, Alvaro, Avery, Christy L, Bandinelli, Stefania, Benjamin, Emelia J, Cucca, Francesco, Dörr, Marcus, and Ferrucci, Luigi
Abstract: Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
Published: 2018

11. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikainen, Leo-Pekka, Mueller, Christian, Mueller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kahonen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J. F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Aldana, Claudia T. Silva, Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Westra, Harm Jan, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Doerr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kaeaeb, Stefan, Lehtimaki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I. W., Isaacs, Aaron, Arking, Dan E., Sotoodehnia, Nona, van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikainen, Leo-Pekka, Mueller, Christian, Mueller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kahonen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J. F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Aldana, Claudia T. Silva, Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Westra, Harm Jan, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Doerr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kaeaeb, Stefan, Lehtimaki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I. W., Isaacs, Aaron, Arking, Dan E., and Sotoodehnia, Nona
Abstract: Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
Published: 2018
Full Text: View/download PDF

12. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: Researchbureau DHL, Onderzoek Precision medicine, Circulatory Health, Genetica, Epi Kanker Team B, Infection & Immunity, van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikäinen, Leo Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J.F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Silva Aldana, Claudia T., Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Dörr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kääb, Stefan, Lehtimäki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I.W., Isaacs, Aaron, Arking, Dan E., Sotoodehnia, Nona, Researchbureau DHL, Onderzoek Precision medicine, Circulatory Health, Genetica, Epi Kanker Team B, Infection & Immunity, van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikäinen, Leo Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J.F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Silva Aldana, Claudia T., Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Dörr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kääb, Stefan, Lehtimäki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I.W., Isaacs, Aaron, Arking, Dan E., and Sotoodehnia, Nona
Published: 2018

13. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikainen, Leo-Pekka, Mueller, Christian, Mueller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kahonen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J. F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Aldana, Claudia T. Silva, Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Westra, Harm Jan, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Doerr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kaeaeb, Stefan, Lehtimaki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I. W., Isaacs, Aaron, Arking, Dan E., Sotoodehnia, Nona, van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikainen, Leo-Pekka, Mueller, Christian, Mueller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, Smith, Albert V., Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O., Asselbergs, Folkert W., Bader, Joel S., Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M., Chung, Mina K., Crawford, Dana, den Hoed, Marcel, Denny, Josh C., Dominiczak, Anna F., Ehret, Georg B., Eijgelsheim, Mark, Ellinor, Patrick T., Felix, Stephan B., Franco, Oscar H., Franke, Lude, Harris, Tamara B., Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kahonen, Mika, Kolcic, Ivana, Kors, Jan A., Lakatta, Edward G., Launer, Lenore J., Lin, Honghuang, Lin, Henry J., Loos, Ruth J. F., Lubitz, Steven A., Macfarlane, Peter W., Magnani, Jared W., Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D., Munzel, Thomas, Papanicolaou, George J., Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P., Raitakari, Olli T., Rotter, Jerome I., Rudan, Igor, Samani, Nilesh J., Schlessinger, David, Aldana, Claudia T. Silva, Sinner, Moritz F., Smith, Jonathan D., Snieder, Harold, Soliman, Elsayed Z., Spector, Timothy D., Stott, David J., Strauch, Konstantin, Tarasov, Kirill V., Thorsteinsdottir, Unnur, Uitterlinden, Andre G., Van Wagoner, David R., Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Westra, Harm Jan, Wild, Philipp S., Zeller, Tanja, Alonso, Alvaro, Avery, Christy L., Bandinelli, Stefania, Benjamin, Emelia J., Cucca, Francesco, Doerr, Marcus, Ferrucci, Luigi, Gasparini, Paolo, Gudnason, Vilmundur, Hayward, Caroline, Heckbert, Susan R., Hicks, Andrew A., Jukema, J. Wouter, Kaeaeb, Stefan, Lehtimaki, Terho, Liu, Yongmei, Munroe, Patricia B., Parsa, Afshin, Polasek, Ozren, Psaty, Bruce M., Roden, Dan M., Schnabel, Renate B., Sinagra, Gianfranco, Stefansson, Kari, Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Wilson, James F., Gharib, Sina A., de Bakker, Paul I. W., Isaacs, Aaron, Arking, Dan E., and Sotoodehnia, Nona
Abstract: Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
Published: 2018
Full Text: View/download PDF

14. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikainen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, Andre G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriette, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J. M., Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikainen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, Andre G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriette, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J. M., Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Abstract: Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
Published: 2017
Full Text: View/download PDF

15. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikainen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, Andre G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriette, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J. M., Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikainen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, Andre G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriette, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J. M., Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Abstract: Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
Published: 2017
Full Text: View/download PDF

16. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikainen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, Andre G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriette, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J. M., Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikainen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, Andre G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriette, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J. M., Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Abstract: Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
Published: 2017
Full Text: View/download PDF

17. Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

Author: Nolte, Ilja M, Nolte, Ilja M, Munoz, M Loretto, Tragante, Vinicius, Amare, Azmeraw T, Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L, Bis, Joshua C, Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M, Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P, Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X, Minassian, Arpi, van der Most, Peter J, Müller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D, Thayer, Julian F, Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G, de Bakker, Paul IW, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J, Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R, Christophersen, Ingrid, Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F, Floras, John S, Franco, Oscar H, Friberg, Peter, Gademan, Maaike GJ, Geyer, Mark A, Giedraitis, Vilmantas, Hartman, Catharina A, Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M, Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C, Lefrandt, Joop D, Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C, Lin, Henry J, Lindgren, Cecilia M, Lubitz, Steven A, Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P, Nalls, Mike A, Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E, O'Connor, Daniel T, Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M, Nolte, Ilja M, Nolte, Ilja M, Munoz, M Loretto, Tragante, Vinicius, Amare, Azmeraw T, Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L, Bis, Joshua C, Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M, Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P, Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X, Minassian, Arpi, van der Most, Peter J, Müller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D, Thayer, Julian F, Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G, de Bakker, Paul IW, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J, Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R, Christophersen, Ingrid, Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F, Floras, John S, Franco, Oscar H, Friberg, Peter, Gademan, Maaike GJ, Geyer, Mark A, Giedraitis, Vilmantas, Hartman, Catharina A, Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M, Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C, Lefrandt, Joop D, Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C, Lin, Henry J, Lindgren, Cecilia M, Lubitz, Steven A, Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P, Nalls, Mike A, Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E, O'Connor, Daniel T, Ormel, Johan, Perz, Siegfried, Peters, Annette, and Psaty, Bruce M
Abstract: Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74g<-0.55) and blood pressure (-0.35g<-0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
Published: 2017

18. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, Van Der Laan, Sander W., Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., De Bakker, Paul I.W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Meyer Zu Schwabedissen, Henriette, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., Van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W., Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, Van Der Laan, Sander W., Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., De Bakker, Paul I.W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Meyer Zu Schwabedissen, Henriette, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., Van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W., Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Published: 2017

19. Erratum : Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I W, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W, Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I W, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W, Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Published: 2017

20. Erratum : Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I W, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W, Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I W, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W, Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Published: 2017

21. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, Van Der Laan, Sander W., Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., De Bakker, Paul I.W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Meyer Zu Schwabedissen, Henriette, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., Van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W., Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, Van Der Laan, Sander W., Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., De Bakker, Paul I.W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Meyer Zu Schwabedissen, Henriette, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., Van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W., Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Published: 2017

22. Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

Author: Nolte, Ilja M, Nolte, Ilja M, Munoz, M Loretto, Tragante, Vinicius, Amare, Azmeraw T, Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L, Bis, Joshua C, Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M, Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P, Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X, Minassian, Arpi, van der Most, Peter J, Müller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D, Thayer, Julian F, Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G, de Bakker, Paul IW, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J, Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R, Christophersen, Ingrid, Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F, Floras, John S, Franco, Oscar H, Friberg, Peter, Gademan, Maaike GJ, Geyer, Mark A, Giedraitis, Vilmantas, Hartman, Catharina A, Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M, Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C, Lefrandt, Joop D, Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C, Lin, Henry J, Lindgren, Cecilia M, Lubitz, Steven A, Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P, Nalls, Mike A, Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E, O'Connor, Daniel T, Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M, Nolte, Ilja M, Nolte, Ilja M, Munoz, M Loretto, Tragante, Vinicius, Amare, Azmeraw T, Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L, Bis, Joshua C, Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M, Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P, Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X, Minassian, Arpi, van der Most, Peter J, Müller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D, Thayer, Julian F, Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G, de Bakker, Paul IW, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J, Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R, Christophersen, Ingrid, Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F, Floras, John S, Franco, Oscar H, Friberg, Peter, Gademan, Maaike GJ, Geyer, Mark A, Giedraitis, Vilmantas, Hartman, Catharina A, Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M, Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C, Lefrandt, Joop D, Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C, Lin, Henry J, Lindgren, Cecilia M, Lubitz, Steven A, Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P, Nalls, Mike A, Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E, O'Connor, Daniel T, Ormel, Johan, Perz, Siegfried, Peters, Annette, and Psaty, Bruce M
Abstract: Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74g<-0.55) and blood pressure (-0.35g<-0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
Published: 2017

23. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, Van Der Laan, Sander W., Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., De Bakker, Paul I.W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Meyer Zu Schwabedissen, Henriette, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., Van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W., Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, Van Der Laan, Sander W., Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., De Bakker, Paul I.W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Meyer Zu Schwabedissen, Henriette, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., Van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W., Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Published: 2017

24. Erratum : Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I W, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W, Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I W, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W, Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Published: 2017

25. Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium.

Author: Weng, Lu-Chen, Weng, Lu-Chen, Lunetta, Kathryn L, Müller-Nurasyid, Martina, Smith, Albert Vernon, Thériault, Sébastien, Weeke, Peter E, Barnard, John, Bis, Joshua C, Lyytikäinen, Leo-Pekka, Kleber, Marcus E, Martinsson, Andreas, Lin, Henry J, Rienstra, Michiel, Trompet, Stella, Krijthe, Bouwe P, Dörr, Marcus, Klarin, Derek, Chasman, Daniel I, Sinner, Moritz F, Waldenberger, Melanie, Launer, Lenore J, Harris, Tamara B, Soliman, Elsayed Z, Alonso, Alvaro, Paré, Guillaume, Teixeira, Pedro L, Denny, Joshua C, Shoemaker, M Benjamin, Van Wagoner, David R, Smith, Jonathan D, Psaty, Bruce M, Sotoodehnia, Nona, Taylor, Kent D, Kähönen, Mika, Nikus, Kjell, Delgado, Graciela E, Melander, Olle, Engström, Gunnar, Yao, Jie, Guo, Xiuqing, Christophersen, Ingrid E, Ellinor, Patrick T, Geelhoed, Bastiaan, Verweij, Niek, Macfarlane, Peter, Ford, Ian, Heeringa, Jan, Franco, Oscar H, Uitterlinden, André G, Völker, Uwe, Teumer, Alexander, Rose, Lynda M, Kääb, Stefan, Gudnason, Vilmundur, Arking, Dan E, Conen, David, Roden, Dan M, Chung, Mina K, Heckbert, Susan R, Benjamin, Emelia J, Lehtimäki, Terho, März, Winfried, Smith, J Gustav, Rotter, Jerome I, van der Harst, Pim, Jukema, J Wouter, Stricker, Bruno H, Felix, Stephan B, Albert, Christine M, Lubitz, Steven A, Weng, Lu-Chen, Weng, Lu-Chen, Lunetta, Kathryn L, Müller-Nurasyid, Martina, Smith, Albert Vernon, Thériault, Sébastien, Weeke, Peter E, Barnard, John, Bis, Joshua C, Lyytikäinen, Leo-Pekka, Kleber, Marcus E, Martinsson, Andreas, Lin, Henry J, Rienstra, Michiel, Trompet, Stella, Krijthe, Bouwe P, Dörr, Marcus, Klarin, Derek, Chasman, Daniel I, Sinner, Moritz F, Waldenberger, Melanie, Launer, Lenore J, Harris, Tamara B, Soliman, Elsayed Z, Alonso, Alvaro, Paré, Guillaume, Teixeira, Pedro L, Denny, Joshua C, Shoemaker, M Benjamin, Van Wagoner, David R, Smith, Jonathan D, Psaty, Bruce M, Sotoodehnia, Nona, Taylor, Kent D, Kähönen, Mika, Nikus, Kjell, Delgado, Graciela E, Melander, Olle, Engström, Gunnar, Yao, Jie, Guo, Xiuqing, Christophersen, Ingrid E, Ellinor, Patrick T, Geelhoed, Bastiaan, Verweij, Niek, Macfarlane, Peter, Ford, Ian, Heeringa, Jan, Franco, Oscar H, Uitterlinden, André G, Völker, Uwe, Teumer, Alexander, Rose, Lynda M, Kääb, Stefan, Gudnason, Vilmundur, Arking, Dan E, Conen, David, Roden, Dan M, Chung, Mina K, Heckbert, Susan R, Benjamin, Emelia J, Lehtimäki, Terho, März, Winfried, Smith, J Gustav, Rotter, Jerome I, van der Harst, Pim, Jukema, J Wouter, Stricker, Bruno H, Felix, Stephan B, Albert, Christine M, and Lubitz, Steven A
Abstract: It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10-5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10-8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.
Published: 2017

26. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikainen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, Andre G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriette, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J. M., Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikainen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, Andre G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriette, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J. M., Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Abstract: Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
Published: 2017
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27. Erratum: Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Circulatory Health, Onderzoek Precision medicine, Experimentele Afd. Cardiologie 1, CMM Groep Kaaij, Infection & Immunity, Aios en Stafsecr. Cardiologie, Team Medisch, Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I W, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W, Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Circulatory Health, Onderzoek Precision medicine, Experimentele Afd. Cardiologie 1, CMM Groep Kaaij, Infection & Immunity, Aios en Stafsecr. Cardiologie, Team Medisch, Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I W, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W, Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Published: 2017

28. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Aios en Stafsecr. Cardiologie, Circulatory Health, Onderzoek Precision medicine, Experimentele Afd. Cardiologie 1, Genetica, Cardiovasculaire Epi Team 7a, CMM Groep Kaaij, Infection & Immunity, Team Medisch, Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, Van Der Laan, Sander W., Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., De Bakker, Paul I.W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Meyer Zu Schwabedissen, Henriette, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., Van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W., Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Aios en Stafsecr. Cardiologie, Circulatory Health, Onderzoek Precision medicine, Experimentele Afd. Cardiologie 1, Genetica, Cardiovasculaire Epi Team 7a, CMM Groep Kaaij, Infection & Immunity, Team Medisch, Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, Von Der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, Van Der Laan, Sander W., Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel G, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad Hadi, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram N, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., De Bakker, Paul I.W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret I., Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G.J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki V., Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun R., Liao, Duanping, Limacher, Marian C., Lin, Henry J, Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, Meyer Zu Schwabedissen, Henriette, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan J., Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F, Siscovick, David S., Smit, Johannes H, Smith, Nicholas L., Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., Van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K, Greiser, Karin Halina, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J, Oldehinkel, Albertine J., Penninx, Brenda Wjh, Reiner, Alexander P, Riese, Harriëtte, Van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G M, Asselbergs, Folkert W., Brundel, Bianca J.J.M., Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Published: 2017

29. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikainen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, Andre G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriette, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J. M., Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikainen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid E., Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, Andre G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriette, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J. M., Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.
Abstract: Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
Published: 2017
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30. Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium.

Author: Bis, Joshua C, Bis, Joshua C, Sitlani, Colleen, Irvin, Ryan, Avery, Christy L, Smith, Albert Vernon, Sun, Fangui, Evans, Daniel S, Musani, Solomon K, Li, Xiaohui, Trompet, Stella, Krijthe, Bouwe P, Harris, Tamara B, Quibrera, P Miguel, Brody, Jennifer A, Demissie, Serkalem, Davis, Barry R, Wiggins, Kerri L, Tranah, Gregory J, Lange, Leslie A, Sotoodehnia, Nona, Stott, David J, Franco, Oscar H, Launer, Lenore J, Stürmer, Til, Taylor, Kent D, Cupples, L Adrienne, Eckfeldt, John H, Smith, Nicholas L, Liu, Yongmei, Wilson, James G, Heckbert, Susan R, Buckley, Brendan M, Ikram, M Arfan, Boerwinkle, Eric, Chen, Yii-Der Ida, de Craen, Anton JM, Uitterlinden, Andre G, Rotter, Jerome I, Ford, Ian, Hofman, Albert, Sattar, Naveed, Slagboom, P Eline, Westendorp, Rudi GJ, Gudnason, Vilmundur, Vasan, Ramachandran S, Lumley, Thomas, Cummings, Steven R, Taylor, Herman A, Post, Wendy, Jukema, J Wouter, Stricker, Bruno H, Whitsel, Eric A, Psaty, Bruce M, Arnett, Donna, Bis, Joshua C, Bis, Joshua C, Sitlani, Colleen, Irvin, Ryan, Avery, Christy L, Smith, Albert Vernon, Sun, Fangui, Evans, Daniel S, Musani, Solomon K, Li, Xiaohui, Trompet, Stella, Krijthe, Bouwe P, Harris, Tamara B, Quibrera, P Miguel, Brody, Jennifer A, Demissie, Serkalem, Davis, Barry R, Wiggins, Kerri L, Tranah, Gregory J, Lange, Leslie A, Sotoodehnia, Nona, Stott, David J, Franco, Oscar H, Launer, Lenore J, Stürmer, Til, Taylor, Kent D, Cupples, L Adrienne, Eckfeldt, John H, Smith, Nicholas L, Liu, Yongmei, Wilson, James G, Heckbert, Susan R, Buckley, Brendan M, Ikram, M Arfan, Boerwinkle, Eric, Chen, Yii-Der Ida, de Craen, Anton JM, Uitterlinden, Andre G, Rotter, Jerome I, Ford, Ian, Hofman, Albert, Sattar, Naveed, Slagboom, P Eline, Westendorp, Rudi GJ, Gudnason, Vilmundur, Vasan, Ramachandran S, Lumley, Thomas, Cummings, Steven R, Taylor, Herman A, Post, Wendy, Jukema, J Wouter, Stricker, Bruno H, Whitsel, Eric A, Psaty, Bruce M, and Arnett, Donna
Abstract: BackgroundHypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.MethodsUsing a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).ResultsAlthough drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the
Published: 2015

31. Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium.

Author: Bis, Joshua C, Pizzi, Carmine1, Bis, Joshua C, Sitlani, Colleen, Irvin, Ryan, Avery, Christy L, Smith, Albert Vernon, Sun, Fangui, Evans, Daniel S, Musani, Solomon K, Li, Xiaohui, Trompet, Stella, Krijthe, Bouwe P, Harris, Tamara B, Quibrera, P Miguel, Brody, Jennifer A, Demissie, Serkalem, Davis, Barry R, Wiggins, Kerri L, Tranah, Gregory J, Lange, Leslie A, Sotoodehnia, Nona, Stott, David J, Franco, Oscar H, Launer, Lenore J, Stürmer, Til, Taylor, Kent D, Cupples, L Adrienne, Eckfeldt, John H, Smith, Nicholas L, Liu, Yongmei, Wilson, James G, Heckbert, Susan R, Buckley, Brendan M, Ikram, M Arfan, Boerwinkle, Eric, Chen, Yii-Der Ida, de Craen, Anton JM, Uitterlinden, Andre G, Rotter, Jerome I, Ford, Ian, Hofman, Albert, Sattar, Naveed, Slagboom, P Eline, Westendorp, Rudi GJ, Gudnason, Vilmundur, Vasan, Ramachandran S, Lumley, Thomas, Cummings, Steven R, Taylor, Herman A, Post, Wendy, Jukema, J Wouter, Stricker, Bruno H, Whitsel, Eric A, Psaty, Bruce M, Arnett, Donna, Bis, Joshua C, Pizzi, Carmine1, Bis, Joshua C, Sitlani, Colleen, Irvin, Ryan, Avery, Christy L, Smith, Albert Vernon, Sun, Fangui, Evans, Daniel S, Musani, Solomon K, Li, Xiaohui, Trompet, Stella, Krijthe, Bouwe P, Harris, Tamara B, Quibrera, P Miguel, Brody, Jennifer A, Demissie, Serkalem, Davis, Barry R, Wiggins, Kerri L, Tranah, Gregory J, Lange, Leslie A, Sotoodehnia, Nona, Stott, David J, Franco, Oscar H, Launer, Lenore J, Stürmer, Til, Taylor, Kent D, Cupples, L Adrienne, Eckfeldt, John H, Smith, Nicholas L, Liu, Yongmei, Wilson, James G, Heckbert, Susan R, Buckley, Brendan M, Ikram, M Arfan, Boerwinkle, Eric, Chen, Yii-Der Ida, de Craen, Anton JM, Uitterlinden, Andre G, Rotter, Jerome I, Ford, Ian, Hofman, Albert, Sattar, Naveed, Slagboom, P Eline, Westendorp, Rudi GJ, Gudnason, Vilmundur, Vasan, Ramachandran S, Lumley, Thomas, Cummings, Steven R, Taylor, Herman A, Post, Wendy, Jukema, J Wouter, Stricker, Bruno H, Whitsel, Eric A, Psaty, Bruce M, and Arnett, Donna
Abstract: BackgroundHypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.MethodsUsing a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).ResultsAlthough drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the
Published: 2015

32. Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease:A Pharmacogenomics Study from the CHARGE Consortium

Author: Bis, Joshua C, Sitlani, Colleen, Irvin, Ryan, Avery, Christy L, Smith, Albert Vernon, Sun, Fangui, Evans, Daniel S, Musani, Solomon K, Li, Xiaohui, Trompet, Stella, Krijthe, Bouwe P, Harris, Tamara B, Quibrera, P Miguel, Brody, Jennifer A, Demissie, Serkalem, Davis, Barry R, Wiggins, Kerri L, Tranah, Gregory J, Lange, Leslie A, Sotoodehnia, Nona, Stott, David J, Franco, Oscar H, Launer, Lenore J, Stürmer, Til, Taylor, Kent D, Cupples, L Adrienne, Eckfeldt, John H, Smith, Nicholas L, Liu, Yongmei, Wilson, James G, Heckbert, Susan R, Buckley, Brendan M, Ikram, M Arfan, Boerwinkle, Eric, Chen, Yii-Der Ida, de Craen, Anton J M, Uitterlinden, Andre G, Rotter, Jerome I, Ford, Ian, Hofman, Albert, Sattar, Naveed, Slagboom, P Eline, Westendorp, Rudi G J, Gudnason, Vilmundur, Vasan, Ramachandran S, Lumley, Thomas, Cummings, Steven R, Taylor, Herman A, Post, Wendy, Jukema, J Wouter, Stricker, Bruno H, Whitsel, Eric A, Psaty, Bruce M, Arnett, Donna, Bis, Joshua C, Sitlani, Colleen, Irvin, Ryan, Avery, Christy L, Smith, Albert Vernon, Sun, Fangui, Evans, Daniel S, Musani, Solomon K, Li, Xiaohui, Trompet, Stella, Krijthe, Bouwe P, Harris, Tamara B, Quibrera, P Miguel, Brody, Jennifer A, Demissie, Serkalem, Davis, Barry R, Wiggins, Kerri L, Tranah, Gregory J, Lange, Leslie A, Sotoodehnia, Nona, Stott, David J, Franco, Oscar H, Launer, Lenore J, Stürmer, Til, Taylor, Kent D, Cupples, L Adrienne, Eckfeldt, John H, Smith, Nicholas L, Liu, Yongmei, Wilson, James G, Heckbert, Susan R, Buckley, Brendan M, Ikram, M Arfan, Boerwinkle, Eric, Chen, Yii-Der Ida, de Craen, Anton J M, Uitterlinden, Andre G, Rotter, Jerome I, Ford, Ian, Hofman, Albert, Sattar, Naveed, Slagboom, P Eline, Westendorp, Rudi G J, Gudnason, Vilmundur, Vasan, Ramachandran S, Lumley, Thomas, Cummings, Steven R, Taylor, Herman A, Post, Wendy, Jukema, J Wouter, Stricker, Bruno H, Whitsel, Eric A, Psaty, Bruce M, and Arnett, Donna
Abstract: BACKGROUND: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.METHODS: Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).RESULTS: Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant
Published: 2015

33. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

Author: Arking, Dan E, Pulit, Sara L, Crotti, Lia, van der Harst, Pim, Munroe, Patricia B, Koopmann, Tamara T, Sotoodehnia, Nona, Rossin, Elizabeth J, Morley, Michael, Wang, Xinchen, Johnson, Andrew D, Lundby, Alicia, Gudbjartsson, Daníel F, Noseworthy, Peter A, Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V, Dörr, Marcus, Müller-Nurasyid, Martina, Lahtinen, Annukka M, Nolte, Ilja M, Smith, Albert Vernon, Bis, Joshua C, Isaacs, Aaron, Newhouse, Stephen J, Evans, Daniel S, Post, Wendy S, Waggott, Daryl, Lyytikäinen, Leo-Pekka, Hicks, Andrew A, Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J, Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W, Naluai, Asa T, Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G, Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A, Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D, Harris, Tamara B, Launer, Lenore J, Shuldiner, Alan R, Alonso, Alvaro, Bader, Joel S, Ehret, Georg, Huang, Hailiang, Kao, W H Linda, Strait, James B, Macfarlane, Peter W, Brown, Morris, Caulfield, Mark J, Samani, Nilesh J, Kronenberg, Florian, Willeit, Johann, Smith, J Gustav, Greiser, Karin H, Meyer Zu Schwabedissen, Henriette, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R, Psaty, Bruce M, Rotter, Jerome I, Kolcic, Ivana, Polašek, Ozren, Wright, Alan F, Griffin, Maura, Daly, Mark J, Arnar, David O, Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C, Roden, Dan M, Zuvich, Rebecca L, Emilsson, Valur, Plump, Andrew S, Larson, Martin G, O'Donnell, Christopher J, Yin, Xiaoyan, Bobbo, Marco, D'Adamo, Adamo P, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R, Nalls, Michael A, Jula, Antti, Kontula, Kimmo K, Marjamaa, Annukka, Oikarinen, Lasse, Perola, Markus, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl-Heinz, Kälsch, Hagen, Nöthen, Markus M, den Hoed, Marcel, Loos, Ruth J F, Thelle, Dag S, Gieger, Christian, Meitinger, Thomas, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F, Waldenberger, Melanie, de Boer, Rudolf A, Franke, Lude, van der Vleuten, Pieter A, Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A M, Behr, Elijah R, Dalageorgou, Chrysoula, Giudicessi, John R, Medeiros-Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M, Scherer, Stephen W, Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E, Greco M, Fabiola Del, Fuchsberger, Christian, O'Connell, Jeffrey R, Lee, Wai K, Watt, Graham C M, Campbell, Harry, Wild, Sarah H, El Mokhtari, Nour E, Frey, Norbert, Asselbergs, Folkert W, Mateo Leach, Irene, Navis, Gerjan, van den Berg, Maarten P, van Veldhuisen, Dirk J, Kellis, Manolis, Krijthe, Bouwe P, Franco, Oscar H, Hofman, Albert, Kors, Jan A, Uitterlinden, André G, Witteman, Jacqueline C M, Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A, Abecasis, Gonçalo R, Lakatta, Edward G, Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R P, Völker, Uwe, Snieder, Harold, Spector, Timothy D, Ärnlöv, Johan, Lind, Lars, Sundström, Johan, Syvänen, Ann-Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T, Viikari, Jorma S, Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N, Paulweber, Bernhard, Haerting, Johannes, Dominiczak, Anna F, Nyberg, Fredrik, Whincup, Peter H, Hingorani, Aroon D, Schott, Jean-Jacques, Bezzina, Connie R, Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F, Rudan, Igor, Franke, Andre, Mühleisen, Thomas W, Pramstaller, Peter P, Lehtimäki, Terho J, Paterson, Andrew D, Parsa, Afshin, Liu, Yongmei, van Duijn, Cornelia M, Siscovick, David S, Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B, Sanna, Serena, Ritchie, Marylyn D, Stricker, Bruno H, Stefansson, Kari, Boyer, Laurie A, Cappola, Thomas P, Olsen, Jesper V, Lage, Kasper, Schwartz, Peter J, Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J, Pfeufer, Arne, de Bakker, Paul I W, Newton-Cheh, Christopher, Arking, Dan E, Pulit, Sara L, Crotti, Lia, van der Harst, Pim, Munroe, Patricia B, Koopmann, Tamara T, Sotoodehnia, Nona, Rossin, Elizabeth J, Morley, Michael, Wang, Xinchen, Johnson, Andrew D, Lundby, Alicia, Gudbjartsson, Daníel F, Noseworthy, Peter A, Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V, Dörr, Marcus, Müller-Nurasyid, Martina, Lahtinen, Annukka M, Nolte, Ilja M, Smith, Albert Vernon, Bis, Joshua C, Isaacs, Aaron, Newhouse, Stephen J, Evans, Daniel S, Post, Wendy S, Waggott, Daryl, Lyytikäinen, Leo-Pekka, Hicks, Andrew A, Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J, Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W, Naluai, Asa T, Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G, Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A, Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D, Harris, Tamara B, Launer, Lenore J, Shuldiner, Alan R, Alonso, Alvaro, Bader, Joel S, Ehret, Georg, Huang, Hailiang, Kao, W H Linda, Strait, James B, Macfarlane, Peter W, Brown, Morris, Caulfield, Mark J, Samani, Nilesh J, Kronenberg, Florian, Willeit, Johann, Smith, J Gustav, Greiser, Karin H, Meyer Zu Schwabedissen, Henriette, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R, Psaty, Bruce M, Rotter, Jerome I, Kolcic, Ivana, Polašek, Ozren, Wright, Alan F, Griffin, Maura, Daly, Mark J, Arnar, David O, Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C, Roden, Dan M, Zuvich, Rebecca L, Emilsson, Valur, Plump, Andrew S, Larson, Martin G, O'Donnell, Christopher J, Yin, Xiaoyan, Bobbo, Marco, D'Adamo, Adamo P, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R, Nalls, Michael A, Jula, Antti, Kontula, Kimmo K, Marjamaa, Annukka, Oikarinen, Lasse, Perola, Markus, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl-Heinz, Kälsch, Hagen, Nöthen, Markus M, den Hoed, Marcel, Loos, Ruth J F, Thelle, Dag S, Gieger, Christian, Meitinger, Thomas, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F, Waldenberger, Melanie, de Boer, Rudolf A, Franke, Lude, van der Vleuten, Pieter A, Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A M, Behr, Elijah R, Dalageorgou, Chrysoula, Giudicessi, John R, Medeiros-Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M, Scherer, Stephen W, Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E, Greco M, Fabiola Del, Fuchsberger, Christian, O'Connell, Jeffrey R, Lee, Wai K, Watt, Graham C M, Campbell, Harry, Wild, Sarah H, El Mokhtari, Nour E, Frey, Norbert, Asselbergs, Folkert W, Mateo Leach, Irene, Navis, Gerjan, van den Berg, Maarten P, van Veldhuisen, Dirk J, Kellis, Manolis, Krijthe, Bouwe P, Franco, Oscar H, Hofman, Albert, Kors, Jan A, Uitterlinden, André G, Witteman, Jacqueline C M, Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A, Abecasis, Gonçalo R, Lakatta, Edward G, Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R P, Völker, Uwe, Snieder, Harold, Spector, Timothy D, Ärnlöv, Johan, Lind, Lars, Sundström, Johan, Syvänen, Ann-Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T, Viikari, Jorma S, Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N, Paulweber, Bernhard, Haerting, Johannes, Dominiczak, Anna F, Nyberg, Fredrik, Whincup, Peter H, Hingorani, Aroon D, Schott, Jean-Jacques, Bezzina, Connie R, Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F, Rudan, Igor, Franke, Andre, Mühleisen, Thomas W, Pramstaller, Peter P, Lehtimäki, Terho J, Paterson, Andrew D, Parsa, Afshin, Liu, Yongmei, van Duijn, Cornelia M, Siscovick, David S, Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B, Sanna, Serena, Ritchie, Marylyn D, Stricker, Bruno H, Stefansson, Kari, Boyer, Laurie A, Cappola, Thomas P, Olsen, Jesper V, Lage, Kasper, Schwartz, Peter J, Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J, Pfeufer, Arne, de Bakker, Paul I W, and Newton-Cheh, Christopher
Abstract: The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
Published: 2014
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34. Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest.

Author: Lemaitre, Rozenn N, Lemaitre, Rozenn N, Johnson, Catherine O, Hesselson, Stephanie, Sotoodehnia, Nona, McKnight, Barbara, Sitlani, Colleen M, Rea, Thomas D, King, Irena B, Kwok, Pui-Yan, Mak, Angel, Li, Guo, Brody, Jennifer, Larson, Eric, Mozaffarian, Dariush, Psaty, Bruce M, Huertas-Vazquez, Adriana, Tardif, Jean-Claude, Albert, Christine M, Lyytikäinen, Leo-Pekka, Arking, Dan E, Kääb, Stefan, Huikuri, Heikki V, Krijthe, Bouwe P, Eijgelsheim, Mark, Wang, Ying A, Reinier, Kyndaron, Lehtimäki, Terho, Pulit, Sara L, Brugada, Ramon, Müller-Nurasyid, Martina, Newton-Cheh, Chris H, Karhunen, Pekka J, Stricker, Bruno H, Goyette, Philippe, Rotter, Jerome I, Chugh, Sumeet S, Chakravarti, Aravinda, Jouven, Xavier, Siscovick, David S, Lemaitre, Rozenn N, Lemaitre, Rozenn N, Johnson, Catherine O, Hesselson, Stephanie, Sotoodehnia, Nona, McKnight, Barbara, Sitlani, Colleen M, Rea, Thomas D, King, Irena B, Kwok, Pui-Yan, Mak, Angel, Li, Guo, Brody, Jennifer, Larson, Eric, Mozaffarian, Dariush, Psaty, Bruce M, Huertas-Vazquez, Adriana, Tardif, Jean-Claude, Albert, Christine M, Lyytikäinen, Leo-Pekka, Arking, Dan E, Kääb, Stefan, Huikuri, Heikki V, Krijthe, Bouwe P, Eijgelsheim, Mark, Wang, Ying A, Reinier, Kyndaron, Lehtimäki, Terho, Pulit, Sara L, Brugada, Ramon, Müller-Nurasyid, Martina, Newton-Cheh, Chris H, Karhunen, Pekka J, Stricker, Bruno H, Goyette, Philippe, Rotter, Jerome I, Chugh, Sumeet S, Chakravarti, Aravinda, Jouven, Xavier, and Siscovick, David S
Abstract: BackgroundThere is limited information on genetic factors associated with sudden cardiac arrest (SCA).ObjectiveTo assess the association of common variation in genes in fatty acid pathways with SCA risk.MethodsWe selected 85 candidate genes and 1155 single nucleotide polymorphisms (SNPs) tagging common variation in each gene. We investigated the SNP associations with SCA in a population-based case-control study. Cases (n = 2160) were from a repository of SCA in the greater Seattle area. Controls (n = 2615), frequency-matched on age and sex, were from the same area. We used linear logistic regression to examine SNP associations with SCA. We performed permutation-based p-min tests to account for multiple comparisons within each gene. The SNP associations with a corrected P value of <.05 were then examined in a meta-analysis of these SNP associations in 9 replication studies totaling 2129 SCA cases and 23,833 noncases.ResultsEight SNPs in or near 8 genes were associated with SCA risk in the discovery study, one of which was nominally significant in the replication phase (rs7737692, minor allele frequency 36%, near the LPCAT1 gene). For each copy of the minor allele, rs7737692 was associated with 13% lower SCA risk (95% confidence interval -21% to -5%) in the discovery phase and 9% lower SCA risk (95% confidence interval -16% to -1%) in the replication phase.ConclusionsWhile none of the associations reached significance with Bonferroni correction, a common genetic variant near LPCAT1, a gene involved in the remodeling of phospholipids, was nominally associated with incident SCA risk. Further study is needed to validate this observation.
Published: 2014

35. Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest.

Author: Lemaitre, Rozenn N, Lemaitre, Rozenn N, Johnson, Catherine O, Hesselson, Stephanie, Sotoodehnia, Nona, McKnight, Barbara, Sitlani, Colleen M, Rea, Thomas D, King, Irena B, Kwok, Pui-Yan, Mak, Angel, Li, Guo, Brody, Jennifer, Larson, Eric, Mozaffarian, Dariush, Psaty, Bruce M, Huertas-Vazquez, Adriana, Tardif, Jean-Claude, Albert, Christine M, Lyytikäinen, Leo-Pekka, Arking, Dan E, Kääb, Stefan, Huikuri, Heikki V, Krijthe, Bouwe P, Eijgelsheim, Mark, Wang, Ying A, Reinier, Kyndaron, Lehtimäki, Terho, Pulit, Sara L, Brugada, Ramon, Müller-Nurasyid, Martina, Newton-Cheh, Chris H, Karhunen, Pekka J, Stricker, Bruno H, Goyette, Philippe, Rotter, Jerome I, Chugh, Sumeet S, Chakravarti, Aravinda, Jouven, Xavier, Siscovick, David S, Lemaitre, Rozenn N, Lemaitre, Rozenn N, Johnson, Catherine O, Hesselson, Stephanie, Sotoodehnia, Nona, McKnight, Barbara, Sitlani, Colleen M, Rea, Thomas D, King, Irena B, Kwok, Pui-Yan, Mak, Angel, Li, Guo, Brody, Jennifer, Larson, Eric, Mozaffarian, Dariush, Psaty, Bruce M, Huertas-Vazquez, Adriana, Tardif, Jean-Claude, Albert, Christine M, Lyytikäinen, Leo-Pekka, Arking, Dan E, Kääb, Stefan, Huikuri, Heikki V, Krijthe, Bouwe P, Eijgelsheim, Mark, Wang, Ying A, Reinier, Kyndaron, Lehtimäki, Terho, Pulit, Sara L, Brugada, Ramon, Müller-Nurasyid, Martina, Newton-Cheh, Chris H, Karhunen, Pekka J, Stricker, Bruno H, Goyette, Philippe, Rotter, Jerome I, Chugh, Sumeet S, Chakravarti, Aravinda, Jouven, Xavier, and Siscovick, David S
Abstract: BackgroundThere is limited information on genetic factors associated with sudden cardiac arrest (SCA).ObjectiveTo assess the association of common variation in genes in fatty acid pathways with SCA risk.MethodsWe selected 85 candidate genes and 1155 single nucleotide polymorphisms (SNPs) tagging common variation in each gene. We investigated the SNP associations with SCA in a population-based case-control study. Cases (n = 2160) were from a repository of SCA in the greater Seattle area. Controls (n = 2615), frequency-matched on age and sex, were from the same area. We used linear logistic regression to examine SNP associations with SCA. We performed permutation-based p-min tests to account for multiple comparisons within each gene. The SNP associations with a corrected P value of <.05 were then examined in a meta-analysis of these SNP associations in 9 replication studies totaling 2129 SCA cases and 23,833 noncases.ResultsEight SNPs in or near 8 genes were associated with SCA risk in the discovery study, one of which was nominally significant in the replication phase (rs7737692, minor allele frequency 36%, near the LPCAT1 gene). For each copy of the minor allele, rs7737692 was associated with 13% lower SCA risk (95% confidence interval -21% to -5%) in the discovery phase and 9% lower SCA risk (95% confidence interval -16% to -1%) in the replication phase.ConclusionsWhile none of the associations reached significance with Bonferroni correction, a common genetic variant near LPCAT1, a gene involved in the remodeling of phospholipids, was nominally associated with incident SCA risk. Further study is needed to validate this observation.
Published: 2014

36. Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese.

Author: Lubitz, Steven A, Lubitz, Steven A, Lunetta, Kathryn L, Lin, Honghuang, Arking, Dan E, Trompet, Stella, Li, Guo, Krijthe, Bouwe P, Chasman, Daniel I, Barnard, John, Kleber, Marcus E, Dörr, Marcus, Ozaki, Kouichi, Smith, Albert V, Müller-Nurasyid, Martina, Walter, Stefan, Agarwal, Sunil K, Bis, Joshua C, Brody, Jennifer A, Chen, Lin Y, Everett, Brendan M, Ford, Ian, Franco, Oscar H, Harris, Tamara B, Hofman, Albert, Kääb, Stefan, Mahida, Saagar, Kathiresan, Sekar, Kubo, Michiaki, Launer, Lenore J, MacFarlane, Peter W, Magnani, Jared W, McKnight, Barbara, McManus, David D, Peters, Annette, Psaty, Bruce M, Rose, Lynda M, Rotter, Jerome I, Silbernagel, Guenther, Smith, Jonathan D, Sotoodehnia, Nona, Stott, David J, Taylor, Kent D, Tomaschitz, Andreas, Tsunoda, Tatsuhiko, Uitterlinden, Andre G, Van Wagoner, David R, Völker, Uwe, Völzke, Henry, Murabito, Joanne M, Sinner, Moritz F, Gudnason, Vilmundur, Felix, Stephan B, März, Winfried, Chung, Mina, Albert, Christine M, Stricker, Bruno H, Tanaka, Toshihiro, Heckbert, Susan R, Jukema, J Wouter, Alonso, Alvaro, Benjamin, Emelia J, Ellinor, Patrick T, Lubitz, Steven A, Lubitz, Steven A, Lunetta, Kathryn L, Lin, Honghuang, Arking, Dan E, Trompet, Stella, Li, Guo, Krijthe, Bouwe P, Chasman, Daniel I, Barnard, John, Kleber, Marcus E, Dörr, Marcus, Ozaki, Kouichi, Smith, Albert V, Müller-Nurasyid, Martina, Walter, Stefan, Agarwal, Sunil K, Bis, Joshua C, Brody, Jennifer A, Chen, Lin Y, Everett, Brendan M, Ford, Ian, Franco, Oscar H, Harris, Tamara B, Hofman, Albert, Kääb, Stefan, Mahida, Saagar, Kathiresan, Sekar, Kubo, Michiaki, Launer, Lenore J, MacFarlane, Peter W, Magnani, Jared W, McKnight, Barbara, McManus, David D, Peters, Annette, Psaty, Bruce M, Rose, Lynda M, Rotter, Jerome I, Silbernagel, Guenther, Smith, Jonathan D, Sotoodehnia, Nona, Stott, David J, Taylor, Kent D, Tomaschitz, Andreas, Tsunoda, Tatsuhiko, Uitterlinden, Andre G, Van Wagoner, David R, Völker, Uwe, Völzke, Henry, Murabito, Joanne M, Sinner, Moritz F, Gudnason, Vilmundur, Felix, Stephan B, März, Winfried, Chung, Mina, Albert, Christine M, Stricker, Bruno H, Tanaka, Toshihiro, Heckbert, Susan R, Jukema, J Wouter, Alonso, Alvaro, Benjamin, Emelia J, and Ellinor, Patrick T
Abstract: ObjectivesThis study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk.BackgroundAF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored.MethodsWe performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases).ResultsWe observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining 8 AF loci. A multilocus score comprised 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements.ConclusionsThe chromosome 4q25 AF locus is architecturally complex and harbors at least 4 AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity.
Published: 2014

37. Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation

Author: Sinner, Moritz F, Tucker, Nathan R, Lunetta, Kathryn L, Ozaki, Kouichi, Smith, J Gustav, Trompet, Stella, Bis, Joshua C, Lin, Honghuang, Chung, Mina K, Nielsen, Jonas B, Lubitz, Steven A, Krijthe, Bouwe P, Magnani, Jared W, Ye, Jiangchuan, Gollob, Michael H, Tsunoda, Tatsuhiko, Müller-Nurasyid, Martina, Lichtner, Peter, Peters, Annette, Dolmatova, Elena, Kubo, Michiaki, Smith, Jonathan D, Psaty, Bruce M, Smith, Nicholas L, Jukema, J Wouter, Chasman, Daniel I, Albert, Christine M, Ebana, Yusuke, Furukawa, Tetsushi, Macfarlane, Peter W, Harris, Tamara B, Darbar, Dawood, Dörr, Marcus, Holst, Anders G, Svendsen, Jesper H, Hofman, Albert, Uitterlinden, Andre G, Gudnason, Vilmundur, Isobe, Mitsuaki, Malik, Rainer, Dichgans, Martin, Rosand, Jonathan, Van Wagoner, David R, Benjamin, Emelia J, Milan, David J, Melander, Olle, Heckbert, Susan R, Ford, Ian, Liu, Yongmei, Olesen, Morten S, Sinner, Moritz F, Tucker, Nathan R, Lunetta, Kathryn L, Ozaki, Kouichi, Smith, J Gustav, Trompet, Stella, Bis, Joshua C, Lin, Honghuang, Chung, Mina K, Nielsen, Jonas B, Lubitz, Steven A, Krijthe, Bouwe P, Magnani, Jared W, Ye, Jiangchuan, Gollob, Michael H, Tsunoda, Tatsuhiko, Müller-Nurasyid, Martina, Lichtner, Peter, Peters, Annette, Dolmatova, Elena, Kubo, Michiaki, Smith, Jonathan D, Psaty, Bruce M, Smith, Nicholas L, Jukema, J Wouter, Chasman, Daniel I, Albert, Christine M, Ebana, Yusuke, Furukawa, Tetsushi, Macfarlane, Peter W, Harris, Tamara B, Darbar, Dawood, Dörr, Marcus, Holst, Anders G, Svendsen, Jesper H, Hofman, Albert, Uitterlinden, Andre G, Gudnason, Vilmundur, Isobe, Mitsuaki, Malik, Rainer, Dichgans, Martin, Rosand, Jonathan, Van Wagoner, David R, Benjamin, Emelia J, Milan, David J, Melander, Olle, Heckbert, Susan R, Ford, Ian, Liu, Yongmei, and Olesen, Morten S
Abstract: BACKGROUND: Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood.METHODS AND RESULTS: To identify new AF-related genes, we used a multifaceted approach, combining large-scale genotyping in 2 ethnically distinct populations, cis-eQTL (expression quantitative trait loci) mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501; relative risk [RR]=1.18; 95% confidence interval [CI], 1.13-1.23; P=6.5×10(-16)), GJA1 (rs13216675; RR=1.10; 95% CI, 1.06-1.14; P=2.2×10(-8)), TBX5 (rs10507248; RR=1.12; 95% CI, 1.08-1.16; P=5.7×10(-11)), and CAND2 (rs4642101; RR=1.10; 95% CI, 1.06-1.14; P=9.8×10(-9)). In Japanese, novel loci were identified near NEURL (rs6584555; RR=1.32; 95% CI, 1.26-1.39; P=2.0×10(-25)) and CUX2 (rs6490029; RR=1.12; 95% CI, 1.08-1.16; P=3.9×10(-9)). The top single-nucleotide polymorphisms or their proxies were identified as cis-eQTLs for the genes CAND2 (P=2.6×10(-19)), GJA1 (P=2.66×10(-6)), and TBX5 (P=1.36×10(-5)). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively).CONCLUSIONS: We have identified 5 novel loci for AF. Our results expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation.
Published: 2014

38. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

Author: Lundby, Alicia, Rossin, Elizabeth J, Steffensen, Annette B, Acha, Moshe Rav, Newton-Cheh, Christopher, Pfeufer, Arne, Lynch, Stacey N, Olesen, Søren-Peter, Brunak, Søren, Ellinor, Patrick T, Jukema, J Wouter, Trompet, Stella, Ford, Ian, Macfarlane, Peter W, Krijthe, Bouwe P, Hofman, Albert, Uitterlinden, André G, Stricker, Bruno H, Nathoe, Hendrik M, Spiering, Wilko, Daly, Mark J, Asselbergs, Folkert W, van der Harst, Pim, Milan, David J, de Bakker, Paul I W, Hansen, Kasper Lage, Olsen, Jesper V, Lundby, Alicia, Rossin, Elizabeth J, Steffensen, Annette B, Acha, Moshe Rav, Newton-Cheh, Christopher, Pfeufer, Arne, Lynch, Stacey N, Olesen, Søren-Peter, Brunak, Søren, Ellinor, Patrick T, Jukema, J Wouter, Trompet, Stella, Ford, Ian, Macfarlane, Peter W, Krijthe, Bouwe P, Hofman, Albert, Uitterlinden, André G, Stricker, Bruno H, Nathoe, Hendrik M, Spiering, Wilko, Daly, Mark J, Asselbergs, Folkert W, van der Harst, Pim, Milan, David J, de Bakker, Paul I W, Hansen, Kasper Lage, and Olsen, Jesper V
Abstract: Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes involved in the Mendelian disorder long QT syndrome (LQTS). We integrated the LQTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LQTS protein network to filter weak GWAS signals by identifying single-nucleotide polymorphisms (SNPs) in proximity to genes in the network supported by strong proteomic evidence. Three SNPs passing this filter reached genome-wide significance after replication genotyping. Overall, we present a general strategy to propose candidates in GWAS loci for functional studies and to systematically filter subtle association signals using tissue-specific quantitative interaction proteomics.
Published: 2014

39. Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation

Author: Sinner, Moritz F, Tucker, Nathan R, Lunetta, Kathryn L, Ozaki, Kouichi, Smith, J Gustav, Trompet, Stella, Bis, Joshua C, Lin, Honghuang, Chung, Mina K, Nielsen, Jonas B, Lubitz, Steven A, Krijthe, Bouwe P, Magnani, Jared W, Ye, Jiangchuan, Gollob, Michael H, Tsunoda, Tatsuhiko, Müller-Nurasyid, Martina, Lichtner, Peter, Peters, Annette, Dolmatova, Elena, Kubo, Michiaki, Smith, Jonathan D, Psaty, Bruce M, Smith, Nicholas L, Jukema, J Wouter, Chasman, Daniel I, Albert, Christine M, Ebana, Yusuke, Furukawa, Tetsushi, Macfarlane, Peter W, Harris, Tamara B, Darbar, Dawood, Dörr, Marcus, Holst, Anders G, Svendsen, Jesper H, Hofman, Albert, Uitterlinden, Andre G, Gudnason, Vilmundur, Isobe, Mitsuaki, Malik, Rainer, Dichgans, Martin, Rosand, Jonathan, Van Wagoner, David R, Benjamin, Emelia J, Milan, David J, Melander, Olle, Heckbert, Susan R, Ford, Ian, Liu, Yongmei, Olesen, Morten S, Sinner, Moritz F, Tucker, Nathan R, Lunetta, Kathryn L, Ozaki, Kouichi, Smith, J Gustav, Trompet, Stella, Bis, Joshua C, Lin, Honghuang, Chung, Mina K, Nielsen, Jonas B, Lubitz, Steven A, Krijthe, Bouwe P, Magnani, Jared W, Ye, Jiangchuan, Gollob, Michael H, Tsunoda, Tatsuhiko, Müller-Nurasyid, Martina, Lichtner, Peter, Peters, Annette, Dolmatova, Elena, Kubo, Michiaki, Smith, Jonathan D, Psaty, Bruce M, Smith, Nicholas L, Jukema, J Wouter, Chasman, Daniel I, Albert, Christine M, Ebana, Yusuke, Furukawa, Tetsushi, Macfarlane, Peter W, Harris, Tamara B, Darbar, Dawood, Dörr, Marcus, Holst, Anders G, Svendsen, Jesper H, Hofman, Albert, Uitterlinden, Andre G, Gudnason, Vilmundur, Isobe, Mitsuaki, Malik, Rainer, Dichgans, Martin, Rosand, Jonathan, Van Wagoner, David R, Benjamin, Emelia J, Milan, David J, Melander, Olle, Heckbert, Susan R, Ford, Ian, Liu, Yongmei, and Olesen, Morten S
Abstract: BACKGROUND: Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood.METHODS AND RESULTS: To identify new AF-related genes, we used a multifaceted approach, combining large-scale genotyping in 2 ethnically distinct populations, cis-eQTL (expression quantitative trait loci) mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501; relative risk [RR]=1.18; 95% confidence interval [CI], 1.13-1.23; P=6.5×10(-16)), GJA1 (rs13216675; RR=1.10; 95% CI, 1.06-1.14; P=2.2×10(-8)), TBX5 (rs10507248; RR=1.12; 95% CI, 1.08-1.16; P=5.7×10(-11)), and CAND2 (rs4642101; RR=1.10; 95% CI, 1.06-1.14; P=9.8×10(-9)). In Japanese, novel loci were identified near NEURL (rs6584555; RR=1.32; 95% CI, 1.26-1.39; P=2.0×10(-25)) and CUX2 (rs6490029; RR=1.12; 95% CI, 1.08-1.16; P=3.9×10(-9)). The top single-nucleotide polymorphisms or their proxies were identified as cis-eQTLs for the genes CAND2 (P=2.6×10(-19)), GJA1 (P=2.66×10(-6)), and TBX5 (P=1.36×10(-5)). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively).CONCLUSIONS: We have identified 5 novel loci for AF. Our results expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation.
Published: 2014

40. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

Author: Lundby, Alicia, Rossin, Elizabeth J, Steffensen, Annette B, Acha, Moshe Rav, Newton-Cheh, Christopher, Pfeufer, Arne, Lynch, Stacey N, Olesen, Søren-Peter, Brunak, Søren, Ellinor, Patrick T, Jukema, J Wouter, Trompet, Stella, Ford, Ian, Macfarlane, Peter W, Krijthe, Bouwe P, Hofman, Albert, Uitterlinden, André G, Stricker, Bruno H, Nathoe, Hendrik M, Spiering, Wilko, Daly, Mark J, Asselbergs, Folkert W, van der Harst, Pim, Milan, David J, de Bakker, Paul I W, Hansen, Kasper Lage, Olsen, Jesper V, Lundby, Alicia, Rossin, Elizabeth J, Steffensen, Annette B, Acha, Moshe Rav, Newton-Cheh, Christopher, Pfeufer, Arne, Lynch, Stacey N, Olesen, Søren-Peter, Brunak, Søren, Ellinor, Patrick T, Jukema, J Wouter, Trompet, Stella, Ford, Ian, Macfarlane, Peter W, Krijthe, Bouwe P, Hofman, Albert, Uitterlinden, André G, Stricker, Bruno H, Nathoe, Hendrik M, Spiering, Wilko, Daly, Mark J, Asselbergs, Folkert W, van der Harst, Pim, Milan, David J, de Bakker, Paul I W, Hansen, Kasper Lage, and Olsen, Jesper V
Abstract: Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes involved in the Mendelian disorder long QT syndrome (LQTS). We integrated the LQTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LQTS protein network to filter weak GWAS signals by identifying single-nucleotide polymorphisms (SNPs) in proximity to genes in the network supported by strong proteomic evidence. Three SNPs passing this filter reached genome-wide significance after replication genotyping. Overall, we present a general strategy to propose candidates in GWAS loci for functional studies and to systematically filter subtle association signals using tissue-specific quantitative interaction proteomics.
Published: 2014

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