Author: "Huang, Paul" / Publication Type: Electronic Resources - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Huang, Paul"' showing total 103 results

Start Over Author "Huang, Paul" Publication Type Electronic Resources

103 results on '"Huang, Paul"'

1. Exploring the Effects of Intersubunit Interface Mutations on Virus-Like Particle Structure and Stability.

Author: Pistono, Paige, Pistono, Paige, Xu, Junyi, Huang, Paul, Fetzer, Jennifer, Francis, Matthew, Pistono, Paige, Pistono, Paige, Xu, Junyi, Huang, Paul, Fetzer, Jennifer, and Francis, Matthew
Abstract: Virus-like particles (VLPs) from bacteriophage MS2 provide a platform to study protein self-assembly and create engineered systems for drug delivery. Here, we aim to understand the impact of intersubunit interface mutations on the local and global structure and function of MS2-based VLPs. In previous work, our lab identified locally supercharged double mutants [T71K/G73R] that concentrate positive charge at capsid pores, enhancing uptake into mammalian cells. To study the effects of particle size on cellular internalization, we combined these double mutants with a single point mutation [S37P] that was previously reported to switch particle geometry from T = 3 to T = 1 icosahedral symmetry. These new variants retained their enhanced cellular uptake activity and could deliver small-molecule drugs with efficacy levels similar to our first-generation capsids. Surprisingly, these engineered triple mutants exhibit increased thermostability and unexpected geometry, producing T = 3 particles instead of the anticipated T = 1 assemblies. Transmission electron microscopy revealed various capsid assembly states, including wild-type (T = 3), T = 1, and rod-like particles, that could be accessed using different combinations of these point mutations. Molecular dynamics experiments recapitulated the structural rationale in silico for the single point mutation [S37P] forming a T = 1 virus-like particle and showed that this assembly state was not favored when combined with mutations that favor rod-like architectures. Through this work, we investigated how interdimer interface dynamics influence VLP size and morphology and how these properties affect particle function in applications such as drug delivery.
Published: 2024

2. Editing the Mind of Giants: An In-Depth Exploration of Pitfalls of Knowledge Editing in Large Language Models

Author: Hsueh, Cheng-Hsun, Huang, Paul Kuo-Ming, Lin, Tzu-Han, Liao, Che-Wei, Fang, Hung-Chieh, Huang, Chao-Wei, Chen, Yun-Nung, Hsueh, Cheng-Hsun, Huang, Paul Kuo-Ming, Lin, Tzu-Han, Liao, Che-Wei, Fang, Hung-Chieh, Huang, Chao-Wei, and Chen, Yun-Nung
Abstract: Knowledge editing is a rising technique for efficiently updating factual knowledge in Large Language Models (LLMs) with minimal alteration of parameters. However, recent studies have identified concerning side effects, such as knowledge distortion and the deterioration of general abilities, that have emerged after editing. This survey presents a comprehensive study of these side effects, providing a unified view of the challenges associated with knowledge editing in LLMs. We discuss related works and summarize potential research directions to overcome these limitations. Our work highlights the limitations of current knowledge editing methods, emphasizing the need for deeper understanding of inner knowledge structures of LLMs and improved knowledge editing methods. To foster future research, we have released the complementary materials such as paper collection publicly at https://github.com/MiuLab/EditLLM-Survey
Published: 2024

3. Face and Content Validity of an Artificial Eye Model for Secondary Intraocular Lens Fixation via Yamane Technique

Author: Huang,Jordan J, Waldner,Derek, Huang,Jaxon J, Huang,Joshua M, Huang,Paul, Teichman,Joshua C, Darvish-Zargar,Mahshad, Gooi,Patrick, Huang,Jordan J, Waldner,Derek, Huang,Jaxon J, Huang,Joshua M, Huang,Paul, Teichman,Joshua C, Darvish-Zargar,Mahshad, and Gooi,Patrick
Abstract: Jordan J Huang,1 Derek Waldner,1,2 Jaxon J Huang,3 Joshua M Huang,1 Paul Huang,1,2 Joshua C Teichman,4,5 Mahshad Darvish-Zargar,6 Patrick Gooi2 1Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 2Division of Ophthalmology, University of Calgary, Calgary, Alberta, Canada; 3John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA; 4Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada; 5Division of Ophthalmology, Trillium Health Partners, Mississauga, Ontario, Canada; 6Division of Ophthalmology, McGill University, Montreal, Quebec, CanadaCorrespondence: Jordan J Huang, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada, Tel +1 403 991 8897, Email jordanhuang8@gmail.comPurpose: To assess the face and content validity of an artificial eye model for secondary intraocular lens (IOL) fixation via the Yamane technique.Methods: Ophthalmologists and residents participated in a 90-minute simulation session on secondary IOL fixation via the Yamane technique. Hands-on practice of this technique was performed on an artificial eye, the Bioniko Okulo BR8. After, all ophthalmologists answered an 18-question survey assessing the face and content validity of the model. Survey responses were recorded on a 5-point double-headed Likert scale, ranging from strongly agree (1)-to-strongly disagree (5) (Figure 1).Results: Twenty-three surveys were completed. Respondents rated the survey with a median response of 1 (strongly agree)-to-3 (neutral). Highest ratings for the model were received for âusefulness for training residentsâ, and âeasier to set up and clean-up compared to a cadaverâ. Lowest ratings were received for realism of the model compared to cadaveric eyes. Statistical analysis revealed no significant difference among identified groups. Ratings for face and content validity were viewed favorably, both with an overall median response of 2.
Published: 2023

4. Prompting and Adapter Tuning for Self-supervised Encoder-Decoder Speech Model

Author: Chang, Kai-Wei, Chen, Ming-Hsin, Lin, Yun-Ping, Hsu, Jing Neng, Huang, Paul Kuo-Ming, Huang, Chien-yu, Li, Shang-Wen, Lee, Hung-yi, Chang, Kai-Wei, Chen, Ming-Hsin, Lin, Yun-Ping, Hsu, Jing Neng, Huang, Paul Kuo-Ming, Huang, Chien-yu, Li, Shang-Wen, and Lee, Hung-yi
Abstract: Prompting and adapter tuning have emerged as efficient alternatives to fine-tuning (FT) methods. However, existing studies on speech prompting focused on classification tasks and failed on more complex sequence generation tasks. Besides, adapter tuning is primarily applied with a focus on encoder-only self-supervised models. Our experiments show that prompting on Wav2Seq, a self-supervised encoder-decoder model, surpasses previous works in sequence generation tasks. It achieves a remarkable 53% relative improvement in word error rate for ASR and a 27% in F1 score for slot filling. Additionally, prompting competes with the FT method in the low-resource scenario. Moreover, we show the transferability of prompting and adapter tuning on Wav2Seq in cross-lingual ASR. When limited trainable parameters are involved, prompting and adapter tuning consistently outperform conventional FT across 7 languages. Notably, in the low-resource scenario, prompting consistently outperforms adapter tuning., Comment: Accepted to IEEE ASRU 2023
Published: 2023

5. Score-based Conditional Generation with Fewer Labeled Data by Self-calibrating Classifier Guidance

Author: Huang, Paul Kuo-Ming, Chen, Si-An, Lin, Hsuan-Tien, Huang, Paul Kuo-Ming, Chen, Si-An, and Lin, Hsuan-Tien
Abstract: Score-based generative models (SGMs) are a popular family of deep generative models that achieve leading image generation quality. Early studies extend SGMs to tackle class-conditional generation by coupling an unconditional SGM with the guidance of a trained classifier. Nevertheless, such classifier-guided SGMs do not always achieve accurate conditional generation, especially when trained with fewer labeled data. We argue that the problem is rooted in the classifier's tendency to overfit without coordinating with the underlying unconditional distribution. To make the classifier respect the unconditional distribution, we propose improving classifier-guided SGMs by letting the classifier regularize itself. The key idea of our proposed method is to use principles from energy-based models to convert the classifier into another view of the unconditional SGM. Existing losses for unconditional SGMs can then be leveraged to achieve regularization by calibrating the classifier's internal unconditional scores. The regularization scheme can be applied to not only the labeled data but also unlabeled ones to further improve the classifier. Across various percentages of fewer labeled data, empirical results show that the proposed approach significantly enhances conditional generation quality. The enhancements confirm the potential of the proposed self-calibration technique for generative modeling with limited labeled data.
Published: 2023

6. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022
Full Text: View/download PDF

7. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022
Full Text: View/download PDF

8. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022
Full Text: View/download PDF

9. A Novel Screw Compressor with a Shunt Enhanced Decompression and Pulsation Trap (SEDAPT)

Author: Huang, Paul Xiubao, Yonkers, Sean, Willie, James, Huang, Paul Xiubao, Yonkers, Sean, and Willie, James
Published: 2022

10. Fitness Landscape-Guided Engineering of Locally Supercharged Virus-like Particles with Enhanced Cell Uptake Properties.

Author: Pistono, Paige E, Pistono, Paige E, Huang, Paul, Brauer, Daniel D, Francis, Matthew B, Pistono, Paige E, Pistono, Paige E, Huang, Paul, Brauer, Daniel D, and Francis, Matthew B
Abstract: Protein-based nanoparticles are useful models for the study of self-assembly and attractive candidates for drug delivery. Virus-like particles (VLPs) are especially promising platforms for expanding the repertoire of therapeutics that can be delivered effectively as they can deliver many copies of a molecule per particle for each delivery event. However, their use is often limited due to poor uptake of VLPs into mammalian cells. In this study, we use the fitness landscape of the bacteriophage MS2 VLP as a guide to engineer capsid variants with positively charged surface residues to enhance their uptake into mammalian cells. By combining mutations with positive fitness scores that were likely to produce assembled capsids, we identified two key double mutants with internalization efficiencies as much as 67-fold higher than that of wtMS2. Internalization of these variants with positively charged surface residues depends on interactions with cell surface sulfated proteoglycans, and yet, they are biophysically similar to wtMS2 with low cytotoxicity and an overall negative charge. Additionally, the best-performing engineered MS2 capsids can deliver a potent anticancer small-molecule therapeutic with efficacy levels similar to antibody-drug conjugates. Through this work, we were able to establish fitness landscape-based engineering as a successful method for designing VLPs with improved cell penetration. These findings suggest that VLPs with positive surface charge could be useful in improving the delivery of small-molecule- and nucleic acid-based therapeutics.
Published: 2022

11. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022
Full Text: View/download PDF

12. A saturated map of common genetic variants associated with human height

Author: Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Partida, Gabriel Cuellar, Sun, Yan, Croteau-Chonka, Damien, Vonk, Judith M., Chanock, Stephen, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., Hirschhorn, Joel N., Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Partida, Gabriel Cuellar, Sun, Yan, Croteau-Chonka, Damien, Vonk, Judith M., Chanock, Stephen, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., and Hirschhorn, Joel N.
Abstract: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
Published: 2022
Full Text: View/download PDF

13. A saturated map of common genetic variants associated with human height

Author: Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Partida, Gabriel Cuellar, Sun, Yan, Croteau-Chonka, Damien, Vonk, Judith M., Chanock, Stephen, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., Hirschhorn, Joel N., Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Partida, Gabriel Cuellar, Sun, Yan, Croteau-Chonka, Damien, Vonk, Judith M., Chanock, Stephen, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., and Hirschhorn, Joel N.
Abstract: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
Published: 2022
Full Text: View/download PDF

14. A saturated map of common genetic variants associated with human height

Author: Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Partida, Gabriel Cuellar, Sun, Yan, Croteau-Chonka, Damien, Vonk, Judith M., Chanock, Stephen, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., Hirschhorn, Joel N., Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Partida, Gabriel Cuellar, Sun, Yan, Croteau-Chonka, Damien, Vonk, Judith M., Chanock, Stephen, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., and Hirschhorn, Joel N.
Abstract: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
Published: 2022
Full Text: View/download PDF

15. A saturated map of common genetic variants associated with human height

Author: Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Partida, Gabriel Cuellar, Sun, Yan, Croteau-Chonka, Damien, Vonk, Judith M., Chanock, Stephen, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., Hirschhorn, Joel N., Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Partida, Gabriel Cuellar, Sun, Yan, Croteau-Chonka, Damien, Vonk, Judith M., Chanock, Stephen, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., and Hirschhorn, Joel N.
Abstract: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
Published: 2022
Full Text: View/download PDF

16. A saturated map of common genetic variants associated with human height

Author: Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Partida, Gabriel Cuellar, Sun, Yan, Croteau-Chonka, Damien, Vonk, Judith M., Chanock, Stephen, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., Hirschhorn, Joel N., Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Partida, Gabriel Cuellar, Sun, Yan, Croteau-Chonka, Damien, Vonk, Judith M., Chanock, Stephen, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., and Hirschhorn, Joel N.
Abstract: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
Published: 2022
Full Text: View/download PDF

17. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan Walter, Haessler, Jeffrey, Lyytikäinen, Leo Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki V., Hutri-Kähönen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo Riitta, Jukema, J. Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J.F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome I., Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan Walter, Haessler, Jeffrey, Lyytikäinen, Leo Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki V., Hutri-Kähönen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo Riitta, Jukema, J. Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J.F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome I., Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022

18. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022
Full Text: View/download PDF

19. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Arts-assistenten Kinderen, Gezonde Vaten, Circulatory Health, Team Medisch, Young, William J, Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A, Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E, Weiss, Stefan, Baldassari, Antoine R, Bartz, Traci M, Cook, James P, Evans, Daniel S, Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L, Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A, Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R, Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C, Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J, Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T, Felix, Stephan B, Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Huang, Paul L, Huikuri, Heikki V, Hutri-Kähönen, Nina, Ikram, M Arfan, Jackson, Rebecca D, Junttila, Juhani, Kavousi, Maryam, Kors, Jan A, Leal, Thiago P, Lemaitre, Rozenn N, Lin, Henry J, Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W, Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P, Mitchell, Rebecca N, Mononen, Nina, Montasser, May E, Morrison, Alanna C, Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K, Pelliccione, Giulia, Pittman, Alan, Porteous, David J, Pramstaller, Peter P, Preuss, Michael H, Raitakari, Olli T, Reiner, Alexander P, Ribeiro, Antonio Luiz P, Rice, Kenneth M, Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M Benjamin, Sinagra, Gianfranco, Sinner, Moritz F, Soliman, Elsayed Z, Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A, Wilson, James G, Avery, Christy L, Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo-Riitta, Jukema, J Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J F, Lubitz, Steven A, Mook-Kanamori, Dennis O, Morris, Andrew P, O'Connell, Jeffrey R, Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M, Rotter, Jerome I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James F, Arking, Dan E, Ramirez, Julia, Lambiase, Pier D, Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B, Arts-assistenten Kinderen, Gezonde Vaten, Circulatory Health, Team Medisch, Young, William J, Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A, Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E, Weiss, Stefan, Baldassari, Antoine R, Bartz, Traci M, Cook, James P, Evans, Daniel S, Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L, Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A, Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R, Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C, Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J, Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T, Felix, Stephan B, Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Huang, Paul L, Huikuri, Heikki V, Hutri-Kähönen, Nina, Ikram, M Arfan, Jackson, Rebecca D, Junttila, Juhani, Kavousi, Maryam, Kors, Jan A, Leal, Thiago P, Lemaitre, Rozenn N, Lin, Henry J, Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W, Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P, Mitchell, Rebecca N, Mononen, Nina, Montasser, May E, Morrison, Alanna C, Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K, Pelliccione, Giulia, Pittman, Alan, Porteous, David J, Pramstaller, Peter P, Preuss, Michael H, Raitakari, Olli T, Reiner, Alexander P, Ribeiro, Antonio Luiz P, Rice, Kenneth M, Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M Benjamin, Sinagra, Gianfranco, Sinner, Moritz F, Soliman, Elsayed Z, Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A, Wilson, James G, Avery, Christy L, Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo-Riitta, Jukema, J Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J F, Lubitz, Steven A, Mook-Kanamori, Dennis O, Morris, Andrew P, O'Connell, Jeffrey R, Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M, Rotter, Jerome I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James F, Arking, Dan E, Ramirez, Julia, Lambiase, Pier D, Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B
Published: 2022

20. Tackling Drug Resistance in EGFR Exon 20 Insertion Mutant Lung Cancer

Author: Pacini,Laura, Jenks,Andrew D, Vyse,Simon, Wilding,Christopher P, Arthur,Amani, Huang,Paul H, Pacini,Laura, Jenks,Andrew D, Vyse,Simon, Wilding,Christopher P, Arthur,Amani, and Huang,Paul H
Abstract: Laura Pacini,* Andrew D Jenks,* Simon Vyse,* Christopher P Wilding, Amani Arthur, Paul H Huang Division of Molecular Pathology, The Institute of Cancer Research, London, UK*These authors contributed equally to this workCorrespondence: Paul H HuangDivision of Molecular Pathology, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UKTel +44 207 153 5554Email paul.huang@icr.ac.ukAbstract: Insertion mutations in exon 20 (Ex20ins) of the epidermal growth factor receptor (EGFR) gene are the largest class of EGFR mutations in non-small cell lung cancer (NSCLC) for which there are currently no approved targeted therapies. NSCLC patients with these mutations do not respond to clinically approved EGFR tyrosine kinase inhibitors (TKIs) and have poor outcomes. A number of early phase clinical trials are currently underway to evaluate the efficacy of a new generation of TKIs that are capable of binding to and blocking Ex20ins. Although these agents have shown some clinical activity, patient responses have been restricted by dose-limiting toxicity or rapid acquisition of resistance after a short response. Here we review the current understanding of the mechanisms of resistance to these compounds, which include on-target EGFR secondary mutations, compensatory bypass pathway activation and acquisition of an EMT phenotype. Taking lessons from conventional EGFR inhibitor therapy in NSCLC, we also consider other potential sources of resistance including the presence of drug-tolerant persister cells. We will discuss therapeutic strategies which have the potential to overcome different forms of drug resistance. We conclude by evaluating recent technological developments in drug discovery such as PROTACs as a means to better tackle TKI resistance in NSCLC harbouring Ex20ins mutations.Keywords: EGFR, exon 20 insertions, poziotinib, lung cancer, drug resistance, PROTACs
Published: 2021

21. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
Full Text: View/download PDF

22. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
Full Text: View/download PDF

23. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
Full Text: View/download PDF

24. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.

Author: Ntalla, Ioanna, Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H, Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R, Choi, Seung Hoan, Chaffin, Mark D, Roselli, Carolina, Barnes, Michael R, Mifsud, Borbala, Warren, Helen R, Hayward, Caroline, Marten, Jonathan, Cranley, James J, Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M, Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P, Souza, Renan P, Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P, Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A, Cook, James P, Lind, Lars, Lindgren, Cecilia M, Sundström, Johan, Nelson, Christopher P, Riaz, Muhammad B, Samani, Nilesh J, Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P, Mononen, Nina, Nikus, Kjell, Caulfield, Mark J, Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E, O'Connell, Jeff R, Ryan, Kathleen, Shuldiner, Alan R, Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Raitakari, Olli T, Barnes, Catriona LK, Campbell, Harry, Joshi, Peter K, Wilson, James F, Isaacs, Aaron, Kors, Jan A, van Duijn, Cornelia M, Huang, Paul L, Gudnason, Vilmundur, Harris, Tamara B, Launer, Lenore J, Smith, Albert V, Bottinger, Erwin P, Loos, Ruth JF, Nadkarni, Girish N, Preuss, Michael H, Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D, Rienstra, Michiel, van de Vegte, Yordi J, van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F, Strauch, Konstantin, Cutler, Michael J, Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M, Ntalla, Ioanna, Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H, Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R, Choi, Seung Hoan, Chaffin, Mark D, Roselli, Carolina, Barnes, Michael R, Mifsud, Borbala, Warren, Helen R, Hayward, Caroline, Marten, Jonathan, Cranley, James J, Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M, Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P, Souza, Renan P, Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P, Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A, Cook, James P, Lind, Lars, Lindgren, Cecilia M, Sundström, Johan, Nelson, Christopher P, Riaz, Muhammad B, Samani, Nilesh J, Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P, Mononen, Nina, Nikus, Kjell, Caulfield, Mark J, Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E, O'Connell, Jeff R, Ryan, Kathleen, Shuldiner, Alan R, Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Raitakari, Olli T, Barnes, Catriona LK, Campbell, Harry, Joshi, Peter K, Wilson, James F, Isaacs, Aaron, Kors, Jan A, van Duijn, Cornelia M, Huang, Paul L, Gudnason, Vilmundur, Harris, Tamara B, Launer, Lenore J, Smith, Albert V, Bottinger, Erwin P, Loos, Ruth JF, Nadkarni, Girish N, Preuss, Michael H, Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D, Rienstra, Michiel, van de Vegte, Yordi J, van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F, Strauch, Konstantin, Cutler, Michael J, Fatkin, Diane, London, Barry, Olesen, Morten, and Roden, Dan M
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
Published: 2020

25. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
Full Text: View/download PDF

26. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.

Author: Ntalla, Ioanna, Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H, Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R, Choi, Seung Hoan, Chaffin, Mark D, Roselli, Carolina, Barnes, Michael R, Mifsud, Borbala, Warren, Helen R, Hayward, Caroline, Marten, Jonathan, Cranley, James J, Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M, Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P, Souza, Renan P, Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P, Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A, Cook, James P, Lind, Lars, Lindgren, Cecilia M, Sundström, Johan, Nelson, Christopher P, Riaz, Muhammad B, Samani, Nilesh J, Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P, Mononen, Nina, Nikus, Kjell, Caulfield, Mark J, Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E, O'Connell, Jeff R, Ryan, Kathleen, Shuldiner, Alan R, Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Raitakari, Olli T, Barnes, Catriona LK, Campbell, Harry, Joshi, Peter K, Wilson, James F, Isaacs, Aaron, Kors, Jan A, van Duijn, Cornelia M, Huang, Paul L, Gudnason, Vilmundur, Harris, Tamara B, Launer, Lenore J, Smith, Albert V, Bottinger, Erwin P, Loos, Ruth JF, Nadkarni, Girish N, Preuss, Michael H, Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D, Rienstra, Michiel, van de Vegte, Yordi J, van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F, Strauch, Konstantin, Cutler, Michael J, Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M, Ntalla, Ioanna, Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H, Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R, Choi, Seung Hoan, Chaffin, Mark D, Roselli, Carolina, Barnes, Michael R, Mifsud, Borbala, Warren, Helen R, Hayward, Caroline, Marten, Jonathan, Cranley, James J, Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M, Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P, Souza, Renan P, Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P, Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A, Cook, James P, Lind, Lars, Lindgren, Cecilia M, Sundström, Johan, Nelson, Christopher P, Riaz, Muhammad B, Samani, Nilesh J, Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P, Mononen, Nina, Nikus, Kjell, Caulfield, Mark J, Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E, O'Connell, Jeff R, Ryan, Kathleen, Shuldiner, Alan R, Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Raitakari, Olli T, Barnes, Catriona LK, Campbell, Harry, Joshi, Peter K, Wilson, James F, Isaacs, Aaron, Kors, Jan A, van Duijn, Cornelia M, Huang, Paul L, Gudnason, Vilmundur, Harris, Tamara B, Launer, Lenore J, Smith, Albert V, Bottinger, Erwin P, Loos, Ruth JF, Nadkarni, Girish N, Preuss, Michael H, Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D, Rienstra, Michiel, van de Vegte, Yordi J, van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F, Strauch, Konstantin, Cutler, Michael J, Fatkin, Diane, London, Barry, Olesen, Morten, and Roden, Dan M
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
Published: 2020

27. Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.

Author: Weng, Lu-Chen, Weng, Lu-Chen, Hall, Amelia Weber, Choi, Seung Hoan, Jurgens, Sean J, Haessler, Jeffrey, Bihlmeyer, Nathan A, Grarup, Niels, Lin, Honghuang, Teumer, Alexander, Li-Gao, Ruifang, Yao, Jie, Guo, Xiuqing, Brody, Jennifer A, Müller-Nurasyid, Martina, Schramm, Katharina, Verweij, Niek, van den Berg, Marten E, van Setten, Jessica, Isaacs, Aaron, Ramírez, Julia, Warren, Helen R, Padmanabhan, Sandosh, Kors, Jan A, de Boer, Rudolf A, van der Meer, Peter, Sinner, Moritz F, Waldenberger, Melanie, Psaty, Bruce M, Taylor, Kent D, Völker, Uwe, Kanters, Jørgen K, Li, Man, Alonso, Alvaro, Perez, Marco V, Vaartjes, Ilonca, Bots, Michiel L, Huang, Paul L, Heckbert, Susan R, Lin, Henry J, Kornej, Jelena, Munroe, Patricia B, van Duijn, Cornelia M, Asselbergs, Folkert W, Stricker, Bruno H, van der Harst, Pim, Kääb, Stefan, Peters, Annette, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Dörr, Marcus, Felix, Stephan B, Linneberg, Allan, Hansen, Torben, Arking, Dan E, Kooperberg, Charles, Benjamin, Emelia J, Lunetta, Kathryn L, Ellinor, Patrick T, Lubitz, Steven A, Weng, Lu-Chen, Weng, Lu-Chen, Hall, Amelia Weber, Choi, Seung Hoan, Jurgens, Sean J, Haessler, Jeffrey, Bihlmeyer, Nathan A, Grarup, Niels, Lin, Honghuang, Teumer, Alexander, Li-Gao, Ruifang, Yao, Jie, Guo, Xiuqing, Brody, Jennifer A, Müller-Nurasyid, Martina, Schramm, Katharina, Verweij, Niek, van den Berg, Marten E, van Setten, Jessica, Isaacs, Aaron, Ramírez, Julia, Warren, Helen R, Padmanabhan, Sandosh, Kors, Jan A, de Boer, Rudolf A, van der Meer, Peter, Sinner, Moritz F, Waldenberger, Melanie, Psaty, Bruce M, Taylor, Kent D, Völker, Uwe, Kanters, Jørgen K, Li, Man, Alonso, Alvaro, Perez, Marco V, Vaartjes, Ilonca, Bots, Michiel L, Huang, Paul L, Heckbert, Susan R, Lin, Henry J, Kornej, Jelena, Munroe, Patricia B, van Duijn, Cornelia M, Asselbergs, Folkert W, Stricker, Bruno H, van der Harst, Pim, Kääb, Stefan, Peters, Annette, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Dörr, Marcus, Felix, Stephan B, Linneberg, Allan, Hansen, Torben, Arking, Dan E, Kooperberg, Charles, Benjamin, Emelia J, Lunetta, Kathryn L, Ellinor, Patrick T, and Lubitz, Steven A
Abstract: BackgroundThe P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD.MethodsFifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies.ResultsWe identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk.ConclusionsOur results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.
Published: 2020

28. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
Full Text: View/download PDF

29. Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation

Author: Weng, Lu Chen, Hall, Amelia Weber, Choi, Seung Hoan, Jurgens, Sean J., Haessler, Jeffrey, Bihlmeyer, Nathan A., Grarup, Niels, Lin, Honghuang, Teumer, Alexander, Li-Gao, Ruifang, Yao, Jie, Guo, Xiuqing, Brody, Jennifer A., Müller-Nurasyid, Martina, Schramm, Katharina, Verweij, Niek, van den Berg, Marten E., van Setten, Jessica, Isaacs, Aaron, Ramírez, Julia, Warren, Helen R., Padmanabhan, Sandosh, Kors, Jan A., de Boer, Rudolf A., van der Meer, Peter, Sinner, Moritz F., Waldenberger, Melanie, Psaty, Bruce M., Taylor, Kent D., Völker, Uwe, Kanters, Jørgen K., Li, Man, Alonso, Alvaro, Perez, Marco V., Vaartjes, Ilonca, Bots, Michiel L., Huang, Paul L., Heckbert, Susan R., Lin, Henry J., Kornej, Jelena, Munroe, Patricia B., van Duijn, Cornelia M., Asselbergs, Folkert W., Stricker, Bruno H., van der Harst, Pim, Kääb, Stefan, Peters, Annette, Sotoodehnia, Nona, Rotter, Jerome I., Mook-Kanamori, Dennis O., Dörr, Marcus, Felix, Stephan B., Linneberg, Allan, Hansen, Torben, Arking, Dan E., Kooperberg, Charles, Benjamin, Emelia J., Lunetta, Kathryn L., Ellinor, Patrick T., Lubitz, Steven A., Weng, Lu Chen, Hall, Amelia Weber, Choi, Seung Hoan, Jurgens, Sean J., Haessler, Jeffrey, Bihlmeyer, Nathan A., Grarup, Niels, Lin, Honghuang, Teumer, Alexander, Li-Gao, Ruifang, Yao, Jie, Guo, Xiuqing, Brody, Jennifer A., Müller-Nurasyid, Martina, Schramm, Katharina, Verweij, Niek, van den Berg, Marten E., van Setten, Jessica, Isaacs, Aaron, Ramírez, Julia, Warren, Helen R., Padmanabhan, Sandosh, Kors, Jan A., de Boer, Rudolf A., van der Meer, Peter, Sinner, Moritz F., Waldenberger, Melanie, Psaty, Bruce M., Taylor, Kent D., Völker, Uwe, Kanters, Jørgen K., Li, Man, Alonso, Alvaro, Perez, Marco V., Vaartjes, Ilonca, Bots, Michiel L., Huang, Paul L., Heckbert, Susan R., Lin, Henry J., Kornej, Jelena, Munroe, Patricia B., van Duijn, Cornelia M., Asselbergs, Folkert W., Stricker, Bruno H., van der Harst, Pim, Kääb, Stefan, Peters, Annette, Sotoodehnia, Nona, Rotter, Jerome I., Mook-Kanamori, Dennis O., Dörr, Marcus, Felix, Stephan B., Linneberg, Allan, Hansen, Torben, Arking, Dan E., Kooperberg, Charles, Benjamin, Emelia J., Lunetta, Kathryn L., Ellinor, Patrick T., and Lubitz, Steven A.
Abstract: BACKGROUND: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. METHODS: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. RESULTS: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk. CONCLUSIONS: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.
Published: 2020

30. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, Ioanna, Weng, Lu Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O’Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo Pekka, Raitakari, Olli T., Barnes, Catriona L.K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert V., Bottinger, Erwin P., Loos, Ruth J.F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Wouter Jukema, J., Macfarlane, Peter W., Trompet, Stella, Dörr, Marcus, Felix, Stephan B., Völker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Sääksjärvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome I., Taylor, Kent D., Yao, Jie, de Mutsert, Renée, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill V., Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, André, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Abdullah Said, M., Yldau van der Ende, M., Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O’Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo Pekka, Raitakari, Olli T., Barnes, Catriona L.K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert V., Bottinger, Erwin P., Loos, Ruth J.F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Wouter Jukema, J., Macfarlane, Peter W., Trompet, Stella, Dörr, Marcus, Felix, Stephan B., Völker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Sääksjärvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome I., Taylor, Kent D., Yao, Jie, de Mutsert, Renée, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill V., Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, André, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Abdullah Said, M., Yldau van der Ende, M., Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
Published: 2020

31. A mouse SWATH-mass spectrometry reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts

Author: The Institute of Cancer Research (UK), Breast Cancer Research Foundation, Medical Research Council (UK), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Research Council, Krasny, Lukas, Bland, Philip, Burns, Jessica, Carvalho Lima, Nadia, Harrison, Peter T., Pacini, Laura, Elms, Mark L., Ning, Jian, Garcia Martinez, Victor, Yu, Yi-Ru, Acton, Sophie E., Ho, Ping-Chih, Calvo, Fernando, Swain, Amanda, Howard, Beatrice A., Natrajan, Rachael C., Huang, Paul H., The Institute of Cancer Research (UK), Breast Cancer Research Foundation, Medical Research Council (UK), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Research Council, Krasny, Lukas, Bland, Philip, Burns, Jessica, Carvalho Lima, Nadia, Harrison, Peter T., Pacini, Laura, Elms, Mark L., Ning, Jian, Garcia Martinez, Victor, Yu, Yi-Ru, Acton, Sophie E., Ho, Ping-Chih, Calvo, Fernando, Swain, Amanda, Howard, Beatrice A., Natrajan, Rachael C., and Huang, Paul H.
Abstract: SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here, we present a comprehensive mouse reference spectral library (MouseRefSWATH) that permits quantification of up to 10,597 proteins (62.2% of the mouse proteome) by SWATH-MS. We exploit MouseRefSWATH to develop an analytical pipeline for species-specific deconvolution of proteomic alterations in human tumour xenografts (XenoSWATH). This method overcomes the challenge of high sequence similarity between mouse and human proteins, facilitating the study of host microenvironment-tumour interactions from ‘bulk tumour’ measurements. We apply the XenoSWATH pipeline to characterize an intraductal xenograft model of breast ductal carcinoma in situ and uncover complex regulation consistent with stromal reprogramming, where the modulation of cell migration pathways is not restricted to tumour cells but also operates in the mouse stroma upon progression to invasive disease. MouseRefSWATH and XenoSWATH open new opportunities for in-depth and reproducible proteomic assessment to address wide-ranging biological questions involving this important model organism.
Published: 2020

32. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
Full Text: View/download PDF

33. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, Ioanna, Weng, Lu Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O’Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo Pekka, Raitakari, Olli T., Barnes, Catriona L.K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert V., Bottinger, Erwin P., Loos, Ruth J.F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Wouter Jukema, J., Macfarlane, Peter W., Trompet, Stella, Dörr, Marcus, Felix, Stephan B., Völker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Sääksjärvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome I., Taylor, Kent D., Yao, Jie, de Mutsert, Renée, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill V., Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, André, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Abdullah Said, M., Yldau van der Ende, M., Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O’Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo Pekka, Raitakari, Olli T., Barnes, Catriona L.K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert V., Bottinger, Erwin P., Loos, Ruth J.F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Wouter Jukema, J., Macfarlane, Peter W., Trompet, Stella, Dörr, Marcus, Felix, Stephan B., Völker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Sääksjärvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome I., Taylor, Kent D., Yao, Jie, de Mutsert, Renée, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill V., Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, André, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Abdullah Said, M., Yldau van der Ende, M., Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
Published: 2020

34. Genetic determinants of electrocardiographic P-wave duration and relation to atrial fibrillation

Author: Researchbureau DHL, Onderzoek Precision medicine, Circulatory Health, RF&S Team 1 Medisch, Cardiovasculaire Epi Team 5, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Team Medisch, AIOS Anesthesiologie, Weng, Lu Chen, Hall, Amelia Weber, Choi, Seung Hoan, Jurgens, Sean J., Haessler, Jeffrey, Bihlmeyer, Nathan A., Grarup, Niels, Lin, Honghuang, Teumer, Alexander, Li-Gao, Ruifang, Yao, Jie, Guo, Xiuqing, Brody, Jennifer A., Müller-Nurasyid, Martina, Schramm, Katharina, Verweij, Niek, van den Berg, Marten E., van Setten, Jessica, Isaacs, Aaron, Ramírez, Julia, Warren, Helen R., Padmanabhan, Sandosh, Kors, Jan A., de Boer, Rudolf A., van der Meer, Peter, Sinner, Moritz F., Waldenberger, Melanie, Psaty, Bruce M., Taylor, Kent D., Völker, Uwe, Kanters, Jørgen K., Li, Man, Alonso, Alvaro, Perez, Marco V., Vaartjes, Ilonca, Bots, Michiel L., Huang, Paul L., Heckbert, Susan R., Lin, Henry J., Kornej, Jelena, Munroe, Patricia B., van Duijn, Cornelia M., Asselbergs, Folkert W., Stricker, Bruno H., van der Harst, Pim, Kääb, Stefan, Peters, Annette, Sotoodehnia, Nona, Rotter, Jerome I., Mook-Kanamori, Dennis O., Researchbureau DHL, Onderzoek Precision medicine, Circulatory Health, RF&S Team 1 Medisch, Cardiovasculaire Epi Team 5, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Team Medisch, AIOS Anesthesiologie, Weng, Lu Chen, Hall, Amelia Weber, Choi, Seung Hoan, Jurgens, Sean J., Haessler, Jeffrey, Bihlmeyer, Nathan A., Grarup, Niels, Lin, Honghuang, Teumer, Alexander, Li-Gao, Ruifang, Yao, Jie, Guo, Xiuqing, Brody, Jennifer A., Müller-Nurasyid, Martina, Schramm, Katharina, Verweij, Niek, van den Berg, Marten E., van Setten, Jessica, Isaacs, Aaron, Ramírez, Julia, Warren, Helen R., Padmanabhan, Sandosh, Kors, Jan A., de Boer, Rudolf A., van der Meer, Peter, Sinner, Moritz F., Waldenberger, Melanie, Psaty, Bruce M., Taylor, Kent D., Völker, Uwe, Kanters, Jørgen K., Li, Man, Alonso, Alvaro, Perez, Marco V., Vaartjes, Ilonca, Bots, Michiel L., Huang, Paul L., Heckbert, Susan R., Lin, Henry J., Kornej, Jelena, Munroe, Patricia B., van Duijn, Cornelia M., Asselbergs, Folkert W., Stricker, Bruno H., van der Harst, Pim, Kääb, Stefan, Peters, Annette, Sotoodehnia, Nona, Rotter, Jerome I., and Mook-Kanamori, Dennis O.
Published: 2020

35. Publisher Correction : Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Author: Turcot, Valérie, Lu, Yingchang, Highland, Heather M, Schurmann, Claudia, Justice, Anne E, Fine, Rebecca S, Bradfield, Jonathan P, Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E, Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E, Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L, Alfred, Tamuno, Feitosa, Mary F, Masca, Nicholas G D, Manning, Alisa K, Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C Y, Reiner, Alex P, Vedantam, Sailaja, Willems, Sara M, Winkler, Thomas W, Abecasis, Gonçalo, Aben, Katja K, Alam, Dewan S, Alharthi, Sameer E, Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bang, Lia E, Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Brumat, Marco, Burt, Amber A, Butterworth, Adam S, Campbell, Peter T, Cappellani, Stefania, Carey, David J, Catamo, Eulalia, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der I, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Crosslin, David S, Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I W, Groot, Mark C H, Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, Heijer, Martin, Hollander, Anneke I, Ruijter, Hester M, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M, Easton, Douglas F, Edwards, Todd L, Ellinghaus, David, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I Sadaf, Faul, Jessica D, Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C, Ford, Ian, Fornage, Myriam, Franco, Oscar H, Franke, Andre, Franks, Paul W, Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P, Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Jörgen, Grant, Struan F A, Grarup, Niels, Griffiths, Helen L, Grove, Megan L, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B, Hattersley, Andrew T, Have, Christian T, Hayward, Caroline, He, Liang, Heard-Costa, Nancy L, Heath, Andrew C, Heid, Iris M, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W, Holmen, Oddgeir L, Hovingh, G Kees, Howson, Joanna M M, Hu, Yao, Huang, Paul L, Huffman, Jennifer E, Ikram, M Arfan, Ingelsson, Erik, Jackson, Anne U, Jansson, Jan-Håkan, Jarvik, Gail P, Jensen, Gorm B, Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E, Jørgensen, Torben, Jukema, J Wouter, Kahali, Bratati, Kahn, René S, Kähönen, Mika, Kamstrup, Pia R, Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L R, Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A, Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S, Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A, Lamparter, David, Lange, Ethan M, Lange, Leslie A, Langenberg, Claudia, Larson, Eric B, Lee, Nanette R, Lehtimäki, Terho, Lewis, Cora E, Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J, Liu, Yongmei, Lo, Ken S, Lophatananon, Artitaya, Lotery, Andrew J, Loukola, Anu, Luan, Jian'an, Lubitz, Steven A, Lyytikäinen, Leo-Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L, McCarthy, Mark I, McKean-Cowdin, Roberta, Medland, Sarah E, Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L, Moilanen, Leena, Moitry, Marie, Montgomery, Grant W, Mook-Kanamori, Dennis O, Moore, Carmel, Mori, Trevor A, Morris, Andrew D, Morris, Andrew P, Müller-Nurasyid, Martina, Munroe, Patricia B, Nalls, Mike A, Narisu, Narisu, Nelson, Christopher P, Neville, Matt, Nielsen, Sune F, Nikus, Kjell, Njølstad, Pål R, Nordestgaard, Børge G, Nyholt, Dale R, O'Connel, Jeffrey R, O'Donoghue, Michelle L, Loohuis, Loes M Olde, Ophoff, Roel A, Owen, Katharine R, Packard, Chris J, Padmanabhan, Sandosh, Palmer, Colin N A, Palmer, Nicholette D, Pasterkamp, Gerard, Patel, Aniruddh P, Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L, Peloso, Gina M, Pennell, Craig E, Perola, Markus, Perry, James A, Perry, John R B, Pers, Tune H, Person, Thomas N, Peters, Annette, Petersen, Eva R B, Peyser, Patricia A, Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J, Puolijoki, Hannu, Raitakari, Olli T, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Renström, Frida, Rheinberger, Myriam, Ridker, Paul M, Rioux, John D, Rivas, Manuel A, Roberts, David J, Robertson, Neil R, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E, Schreiner, Pamela J, Schulze, Matthias B, Scott, Robert A, Segura-Lepe, Marcelo P, Shah, Svati H, Sheu, Wayne H-H, Sim, Xueling, Slater, Andrew J, Small, Kerrin S, Smith, Albert V, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E, Strauch, Konstantin, Stringham, Heather M, Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J, Tada, Hayato, Tansey, Katherine E, Tardif, Jean-Claude, Taylor, Kent D, Teumer, Alexander, Thompson, Deborah J, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H, Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P, Uher, Rudolf, Uitterlinden, André G, Uusitupa, Matti, Laan, Sander W, Duijn, Cornelia M, Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V, Varma, Rohit, Edwards, Digna R Velez, Vermeulen, Sita H, Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F, Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E, Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A, Wang, Shuai, Wang, Yiqin, Ware, Erin B, Wareham, Nicholas J, Warren, Helen R, Waterworth, Dawn M, Wessel, Jennifer, White, Harvey D, Willer, Cristen J, Wilson, James G, Witte, Daniel R, Wood, Andrew R, Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M, Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, Rotter, Jerome I, Pospisilik, John A, Rivadeneira, Fernando, Borecki, Ingrid B, Deloukas, Panos, Frayling, Timothy M, Lettre, Guillaume, North, Kari E, Lindgren, Cecilia M, Hirschhorn, Joel N, Loos, Ruth J F, Turcot, Valérie, Lu, Yingchang, Highland, Heather M, Schurmann, Claudia, Justice, Anne E, Fine, Rebecca S, Bradfield, Jonathan P, Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E, Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E, Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L, Alfred, Tamuno, Feitosa, Mary F, Masca, Nicholas G D, Manning, Alisa K, Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C Y, Reiner, Alex P, Vedantam, Sailaja, Willems, Sara M, Winkler, Thomas W, Abecasis, Gonçalo, Aben, Katja K, Alam, Dewan S, Alharthi, Sameer E, Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bang, Lia E, Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Brumat, Marco, Burt, Amber A, Butterworth, Adam S, Campbell, Peter T, Cappellani, Stefania, Carey, David J, Catamo, Eulalia, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der I, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Crosslin, David S, Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I W, Groot, Mark C H, Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, Heijer, Martin, Hollander, Anneke I, Ruijter, Hester M, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M, Easton, Douglas F, Edwards, Todd L, Ellinghaus, David, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I Sadaf, Faul, Jessica D, Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C, Ford, Ian, Fornage, Myriam, Franco, Oscar H, Franke, Andre, Franks, Paul W, Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P, Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Jörgen, Grant, Struan F A, Grarup, Niels, Griffiths, Helen L, Grove, Megan L, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B, Hattersley, Andrew T, Have, Christian T, Hayward, Caroline, He, Liang, Heard-Costa, Nancy L, Heath, Andrew C, Heid, Iris M, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W, Holmen, Oddgeir L, Hovingh, G Kees, Howson, Joanna M M, Hu, Yao, Huang, Paul L, Huffman, Jennifer E, Ikram, M Arfan, Ingelsson, Erik, Jackson, Anne U, Jansson, Jan-Håkan, Jarvik, Gail P, Jensen, Gorm B, Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E, Jørgensen, Torben, Jukema, J Wouter, Kahali, Bratati, Kahn, René S, Kähönen, Mika, Kamstrup, Pia R, Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L R, Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A, Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S, Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A, Lamparter, David, Lange, Ethan M, Lange, Leslie A, Langenberg, Claudia, Larson, Eric B, Lee, Nanette R, Lehtimäki, Terho, Lewis, Cora E, Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J, Liu, Yongmei, Lo, Ken S, Lophatananon, Artitaya, Lotery, Andrew J, Loukola, Anu, Luan, Jian'an, Lubitz, Steven A, Lyytikäinen, Leo-Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L, McCarthy, Mark I, McKean-Cowdin, Roberta, Medland, Sarah E, Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L, Moilanen, Leena, Moitry, Marie, Montgomery, Grant W, Mook-Kanamori, Dennis O, Moore, Carmel, Mori, Trevor A, Morris, Andrew D, Morris, Andrew P, Müller-Nurasyid, Martina, Munroe, Patricia B, Nalls, Mike A, Narisu, Narisu, Nelson, Christopher P, Neville, Matt, Nielsen, Sune F, Nikus, Kjell, Njølstad, Pål R, Nordestgaard, Børge G, Nyholt, Dale R, O'Connel, Jeffrey R, O'Donoghue, Michelle L, Loohuis, Loes M Olde, Ophoff, Roel A, Owen, Katharine R, Packard, Chris J, Padmanabhan, Sandosh, Palmer, Colin N A, Palmer, Nicholette D, Pasterkamp, Gerard, Patel, Aniruddh P, Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L, Peloso, Gina M, Pennell, Craig E, Perola, Markus, Perry, James A, Perry, John R B, Pers, Tune H, Person, Thomas N, Peters, Annette, Petersen, Eva R B, Peyser, Patricia A, Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J, Puolijoki, Hannu, Raitakari, Olli T, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Renström, Frida, Rheinberger, Myriam, Ridker, Paul M, Rioux, John D, Rivas, Manuel A, Roberts, David J, Robertson, Neil R, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E, Schreiner, Pamela J, Schulze, Matthias B, Scott, Robert A, Segura-Lepe, Marcelo P, Shah, Svati H, Sheu, Wayne H-H, Sim, Xueling, Slater, Andrew J, Small, Kerrin S, Smith, Albert V, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E, Strauch, Konstantin, Stringham, Heather M, Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J, Tada, Hayato, Tansey, Katherine E, Tardif, Jean-Claude, Taylor, Kent D, Teumer, Alexander, Thompson, Deborah J, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H, Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P, Uher, Rudolf, Uitterlinden, André G, Uusitupa, Matti, Laan, Sander W, Duijn, Cornelia M, Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V, Varma, Rohit, Edwards, Digna R Velez, Vermeulen, Sita H, Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F, Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E, Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A, Wang, Shuai, Wang, Yiqin, Ware, Erin B, Wareham, Nicholas J, Warren, Helen R, Waterworth, Dawn M, Wessel, Jennifer, White, Harvey D, Willer, Cristen J, Wilson, James G, Witte, Daniel R, Wood, Andrew R, Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M, Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, Rotter, Jerome I, Pospisilik, John A, Rivadeneira, Fernando, Borecki, Ingrid B, Deloukas, Panos, Frayling, Timothy M, Lettre, Guillaume, North, Kari E, Lindgren, Cecilia M, Hirschhorn, Joel N, and Loos, Ruth J F
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019
Full Text: View/download PDF

36. Parallel vs. Serial Noise Suppression Method for Positive Displacement (PD) Compressors & Internal Combustion Engines (ICE)

Author: Huang, Paul Xiubao, Dr., Groll, Eckhard A, Yonkers, Sean, Huang, Paul Xiubao, Dr., Groll, Eckhard A, and Yonkers, Sean
Abstract: Positive displacement (PD) compressors and internal combustion engines (ICEs) are major energy consumers. For example, a typical US household may have as many as 7 compressors (2 in house AC, 2 in auto AC, 1 each for refrigerator or freezer or shop compressed air) and 4 ICEs (2 in auto, 1 each for lawn mower and auxiliary power generator). However, they both generate high amplitude pulsating pressures1 (up to 180-200 dB) and discharge flows that demand a silencer or muffler to suppress the noise but leads to high energy costs: up to 5-7% shaft power for PD compressors and up to 2-5% gasoline or diesel consumption for ICEs. Growing global demand for higher efficiency and lower noise for these systems is conflicting with the governing rule of serial muffling employed for the past 100 years: “more noise reduction, more back pressure losses or larger sizes”. No current technology could meet both demands simultaneously due to the limitation of the current serial noise suppression methodology. The primary goal of this paper is to demonstrate Shunt Pulsation Trap (SPT) - a parallel noise suppression method that will overcome this limitation and is capable of getting the pulsating noise under control with little back pressure loss and compact size. The SPT technology involves modifications to a standard PD compression cycle from a serial mode, that is, treats or dampens the noise generating source ∆P (Poutlet-Pcavity) after discharge, to a parallel mode before discharge. Thermodynamic analysis and earlier tests on a Roots-type compressor with SPT indicate this novel noise suppression concept yields a substantial saving in shaft power (5-16%) while remaining compact compared with a serial silencer. Parallel and serial noise suppression rules are summarized and applied to various PD type compressors and ICEs.
Published: 2018

37. Multi-ethnic genome-wide association study for atrial fibrillation

Author: Roselli, Carolina, Chaffin, Mark D., Weng, Lu-Chen, Aeschbacher, Stefanie, Ahlberg, Gustav, Albert, Christine M., Almgren, Peter, Alonso, Alvaro, Anderson, Christopher D., Aragam, Krishna G., Arking, Dan E., Barnard, John, Bartz, Traci M., Benjamin, Emelia J., Bihlmeyer, Nathan A., Bis, Joshua C., Bloom, Heather L., Boerwinkle, Eric, Bottinger, Erwin B., Brody, Jennifer A., Calkins, Hugh, Campbell, Archie, Cappola, Thomas P., Carlquist, John, Chasman, Daniel I., Chen, Lin Y., Chen, Yii-Der Ida, Choi, Eue-Keun, Choi, Seung Hoan, Christophersen, Ingrid E., Chung, Mina K., Cole, John W., Conen, David, Cook, James, Crijns, Harry J., Cutler, Michael J., Damrauer, Scott M., Daniels, Brian R., Darbar, Dawood, Delgado, Graciela, Denny, Joshua C., Dichgans, Martin, Doerr, Marcus, Dudink, Elton A., Dudley, Samuel C., Esa, Nada, Esko, Tonu, Eskola, Markku, Fatkin, Diane, Felix, Stephan B., Ford, Ian, Franco, Oscar H., Geelhoed, Bastiaan, Grewal, Raji P., Gudnason, Vilmundur, Guo, Xiuqing, Gupta, Namrata, Gustafsson, Stefan, Gutmann, Rebecca, Hamsten, Anders, Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Hernesniemi, Jussi, Hocking, Lynne J., Hofman, Albert, Horimoto, Andrea R. V. R., Huang, Jie, Huang, Paul L., Huffman, Jennifer, Ingelsson, Erik, Ipek, Esra Gucuk, Ito, Kaoru, Jimenez-Conde, Jordi, Johnson, Renee, Jukema, J. Wouter, Kaeaeb, Stefan, Kahonen, Mika, Kamatani, Yoichiro, Kane, John P., Kastrati, Adnan, Kathiresan, Sekar, Katschnig-Winter, Petra, Kavousi, Maryam, Kessler, Thorsten, Kietselaer, Bas L., Kirchhof, Paulus, Kleber, Marcus E., Knight, Stacey, Krieger, Jose E., Kubo, Michiaki, Launer, Lenore J., Laurikka, Jari, Lehtimaki, Terho, Leineweber, Kirsten, Lemaitre, Rozenn N., Li, Man, Lim, Hong Euy, Lin, Henry J., Lin, Honghuang, Lind, Lars, Lindgren, Cecilia M., Lokki, Marja-Liisa, London, Barry, Loos, Ruth J. F., Low, Siew-Kee, Lu, Yingchang, Lyytikainen, Leo-Pekka, Macfarlane, Peter W., Magnusson, Patrik K., Mahajan, Anubha, Malik, Rainer, Mansur, Alfredo J., Marcus, Gregory M., Margolin, Lauren, Margulies, Kenneth B., Maerz, Winfried, McManus, David D., Melander, Olle, Mohanty, Sanghamitra, Montgomery, Jay A., Morley, Michael P., Morris, Andrew P., Mueller-Nurasyid, Martina, Natale, Andrea, Nazarian, Saman, Neumann, Benjamin, Newton-Cheh, Christopher, Niemeijer, Maartje N., Nikus, Kjell, Nilsson, Peter, Noordam, Raymond, Oellers, Heidi, Olesen, Morten S., Orho-Melander, Marju, Padmanabhan, Sandosh, Pak, Hui-Nam, Pare, Guillaume, Pedersen, Nancy L., Pera, Joanna, Pereira, Alexandre, Porteous, David, Psaty, Bruce M., Pulit, Sara L., Pullinger, Clive R., Rader, Daniel J., Refsgaard, Lena, Ribases, Marta, Ridker, Paul M., Rienstra, Michiel, Risch, Lorenz, Roden, Dan M., Rosand, Jonathan, Rosenberg, Michael A., Rost, Natalia, Rotter, Jerome I., Saba, Samir, Sandhu, Roopinder K., Schnabel, Renate B., Schramm, Katharina, Schunkert, Heribert, Schurman, Claudia, Scott, Stuart A., Seppala, Ilkka, Shaffer, Christian, Shah, Svati, Shalaby, Alaa A., Shim, Jaemin, Shoemaker, M. Benjamin, Siland, Joylene E., Sinisalo, Juha, Sinner, Moritz F., Slowik, Agnieszka, Smith, Albert V., Smith, Blair H., Smith, J. Gustav, Smith, Jonathan D., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Stricker, Bruno H., Sun, Albert, Sun, Han, Svendsen, Jesper H., Tanaka, Toshihiro, Tanriverdi, Kahraman, Taylor, Kent D., Teder-Laving, Maris, Teumer, Alexander, Theriault, Sebastien, Trompet, Stella, Tucker, Nathan R., Tveit, Arnljot, Uitterlinden, Andre G., Van Der Harst, Pim, Van Gelder, Isabelle C., Van Wagoner, David R., Verweij, Niek, Vlachopoulou, Efthymia, Voelker, Uwe, Wang, Biqi, Weeke, Peter E., Weijs, Bob, Weiss, Raul, Weiss, Stefan, Wells, Quinn S., Wiggins, Kerri L., Wong, Jorge A., Woo, Daniel, Worrall, Bradford B., Yang, Pil-Sung, Yao, Jie, Yoneda, Zachary T., Zeller, Tanja, Zeng, Lingyao, Lubitz, Steven A., Lunetta, Kathryn L., Ellinor, Patrick T., Roselli, Carolina, Chaffin, Mark D., Weng, Lu-Chen, Aeschbacher, Stefanie, Ahlberg, Gustav, Albert, Christine M., Almgren, Peter, Alonso, Alvaro, Anderson, Christopher D., Aragam, Krishna G., Arking, Dan E., Barnard, John, Bartz, Traci M., Benjamin, Emelia J., Bihlmeyer, Nathan A., Bis, Joshua C., Bloom, Heather L., Boerwinkle, Eric, Bottinger, Erwin B., Brody, Jennifer A., Calkins, Hugh, Campbell, Archie, Cappola, Thomas P., Carlquist, John, Chasman, Daniel I., Chen, Lin Y., Chen, Yii-Der Ida, Choi, Eue-Keun, Choi, Seung Hoan, Christophersen, Ingrid E., Chung, Mina K., Cole, John W., Conen, David, Cook, James, Crijns, Harry J., Cutler, Michael J., Damrauer, Scott M., Daniels, Brian R., Darbar, Dawood, Delgado, Graciela, Denny, Joshua C., Dichgans, Martin, Doerr, Marcus, Dudink, Elton A., Dudley, Samuel C., Esa, Nada, Esko, Tonu, Eskola, Markku, Fatkin, Diane, Felix, Stephan B., Ford, Ian, Franco, Oscar H., Geelhoed, Bastiaan, Grewal, Raji P., Gudnason, Vilmundur, Guo, Xiuqing, Gupta, Namrata, Gustafsson, Stefan, Gutmann, Rebecca, Hamsten, Anders, Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Hernesniemi, Jussi, Hocking, Lynne J., Hofman, Albert, Horimoto, Andrea R. V. R., Huang, Jie, Huang, Paul L., Huffman, Jennifer, Ingelsson, Erik, Ipek, Esra Gucuk, Ito, Kaoru, Jimenez-Conde, Jordi, Johnson, Renee, Jukema, J. Wouter, Kaeaeb, Stefan, Kahonen, Mika, Kamatani, Yoichiro, Kane, John P., Kastrati, Adnan, Kathiresan, Sekar, Katschnig-Winter, Petra, Kavousi, Maryam, Kessler, Thorsten, Kietselaer, Bas L., Kirchhof, Paulus, Kleber, Marcus E., Knight, Stacey, Krieger, Jose E., Kubo, Michiaki, Launer, Lenore J., Laurikka, Jari, Lehtimaki, Terho, Leineweber, Kirsten, Lemaitre, Rozenn N., Li, Man, Lim, Hong Euy, Lin, Henry J., Lin, Honghuang, Lind, Lars, Lindgren, Cecilia M., Lokki, Marja-Liisa, London, Barry, Loos, Ruth J. F., Low, Siew-Kee, Lu, Yingchang, Lyytikainen, Leo-Pekka, Macfarlane, Peter W., Magnusson, Patrik K., Mahajan, Anubha, Malik, Rainer, Mansur, Alfredo J., Marcus, Gregory M., Margolin, Lauren, Margulies, Kenneth B., Maerz, Winfried, McManus, David D., Melander, Olle, Mohanty, Sanghamitra, Montgomery, Jay A., Morley, Michael P., Morris, Andrew P., Mueller-Nurasyid, Martina, Natale, Andrea, Nazarian, Saman, Neumann, Benjamin, Newton-Cheh, Christopher, Niemeijer, Maartje N., Nikus, Kjell, Nilsson, Peter, Noordam, Raymond, Oellers, Heidi, Olesen, Morten S., Orho-Melander, Marju, Padmanabhan, Sandosh, Pak, Hui-Nam, Pare, Guillaume, Pedersen, Nancy L., Pera, Joanna, Pereira, Alexandre, Porteous, David, Psaty, Bruce M., Pulit, Sara L., Pullinger, Clive R., Rader, Daniel J., Refsgaard, Lena, Ribases, Marta, Ridker, Paul M., Rienstra, Michiel, Risch, Lorenz, Roden, Dan M., Rosand, Jonathan, Rosenberg, Michael A., Rost, Natalia, Rotter, Jerome I., Saba, Samir, Sandhu, Roopinder K., Schnabel, Renate B., Schramm, Katharina, Schunkert, Heribert, Schurman, Claudia, Scott, Stuart A., Seppala, Ilkka, Shaffer, Christian, Shah, Svati, Shalaby, Alaa A., Shim, Jaemin, Shoemaker, M. Benjamin, Siland, Joylene E., Sinisalo, Juha, Sinner, Moritz F., Slowik, Agnieszka, Smith, Albert V., Smith, Blair H., Smith, J. Gustav, Smith, Jonathan D., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Stricker, Bruno H., Sun, Albert, Sun, Han, Svendsen, Jesper H., Tanaka, Toshihiro, Tanriverdi, Kahraman, Taylor, Kent D., Teder-Laving, Maris, Teumer, Alexander, Theriault, Sebastien, Trompet, Stella, Tucker, Nathan R., Tveit, Arnljot, Uitterlinden, Andre G., Van Der Harst, Pim, Van Gelder, Isabelle C., Van Wagoner, David R., Verweij, Niek, Vlachopoulou, Efthymia, Voelker, Uwe, Wang, Biqi, Weeke, Peter E., Weijs, Bob, Weiss, Raul, Weiss, Stefan, Wells, Quinn S., Wiggins, Kerri L., Wong, Jorge A., Woo, Daniel, Worrall, Bradford B., Yang, Pil-Sung, Yao, Jie, Yoneda, Zachary T., Zeller, Tanja, Zeng, Lingyao, Lubitz, Steven A., Lunetta, Kathryn L., and Ellinor, Patrick T.
Abstract: Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
Published: 2018
Full Text: View/download PDF

38. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author: Turcot, Valerie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tonu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Goncalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Ines, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Joergen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Hakan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltan, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mannisto, Satu, Marenne, Gaelle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renstrom, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H. -H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Voelker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., Loos, Ruth J. F., Turcot, Valerie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tonu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Goncalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Ines, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Joergen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Hakan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltan, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mannisto, Satu, Marenne, Gaelle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renstrom, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H. -H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Voelker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., and Loos, Ruth J. F.
Abstract: Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity., Correction in: Nature Genetics https://doi.org/10.1038/s41588-017-0011-x, published online 22 December 2017. Published online: 3 June 2019https://doi.org/10.1038/s41588-019-0447-2
Published: 2018
Full Text: View/download PDF

39. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author: Turcot, Valerie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tonu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Goncalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Ines, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Joergen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltan, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mannisto, Satu, Marenne, Gaelle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H. -H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Voelker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., Loos, Ruth J. F., Turcot, Valerie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tonu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Goncalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Ines, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Joergen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltan, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mannisto, Satu, Marenne, Gaelle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H. -H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Voelker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., and Loos, Ruth J. F.
Abstract: Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity., Corrections:Turcot, V., Lu, Y., Highland, H.M. et al. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat Genet 50, 765–766 (2018). DOI: 10.1038/s41588-018-0050-yTurcot, V., Lu, Y., Highland, H.M. et al. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat Genet 50, 766–767 (2018). DOI: 10.1038/s41588-018-0082-3Turcot, V., Lu, Y., Highland, H.M. et al. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat Genet 51, 1191–1192 (2019). DOI: 10.1038/s41588-019-0447-2
Published: 2018
Full Text: View/download PDF

40. Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval

Author: Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, Isaacs, Aaron, Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, and Isaacs, Aaron
Published: 2018

41. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author: Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., Jamshidi, Yalda, Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., and Jamshidi, Yalda
Published: 2018

42. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals

Author: Bihlmeyer, Nathan A., Brody, Jennifer A., Smith, Albert Vernon, Warren, Helen R., Lin, Honghuang, Isaacs, Aaron, Liu, Ching Ti, Marten, Jonathan, Radmanesh, Farid, Hall, Leanne M., Grarup, Niels, Mei, Hao, Müller-Nurasyid, Martina, Huffman, Jennifer E., Verweij, Niek, Guo, Xiuqing, Yao, Jie, Li-Gao, Ruifang, van den Berg, Marten, Weiss, Stefan, Prins, Bram P., van Setten, Jessica, Haessler, Jeffrey, Lyytikäinen, Leo Pekka, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z., Bis, Joshua C., Austin, Tom, Chen, Yii Der Ida, Psaty, Bruce M., Harrris, Tamara B., Launer, Lenore J., Padmanabhan, Sandosh, Dominiczak, Anna, Huang, Paul L., Xie, Zhijun, Ellinor, Patrick T., Kors, Jan A., Campbell, Archie, Murray, Alison D., Nelson, Christopher P., Tobin, Martin D., Bork-Jensen, Jette, Hansen, Torben, Pedersen, Oluf, Linneberg, Allan, Sinner, Moritz F., Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Perz, Siegfried, Kolcic, Ivana, Rudan, Igor, de Boer, Rudolf A., van der Meer, Peter, Lin, Henry J., Taylor, Kent D., de Mutsert, Renée, Trompet, Stella, Jukema, J. Wouter, Maan, Arie C., Stricker, Bruno H.C., Rivadeneira, Fernando, Uitterlinden, André, Völker, Uwe, Homuth, Georg, Völzke, Henry, Felix, Stephan B., Mangino, Massimo, Spector, Timothy D., Bots, Michiel L., Perez, Marco, Raitakari, Olli T., Kähönen, Mika, Mononen, Nina, Gudnason, Vilmundur, Munroe, Patricia B., Lubitz, Steven A., van Duijn, Cornelia M., Newton-Cheh, Christopher H., Hayward, Caroline, Rosand, Jonathan, Samani, Nilesh J., Kanters, Jørgen K., Wilson, James G., Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R., Rotter, Jerome I., Mook-Kanamori, Dennis O., Eijgelsheim, Mark, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W., Kooperberg, Charles, Lehtimäki, Terho, Arking, Dan E., Sotoodehnia, Nona, Bihlmeyer, Nathan A., Brody, Jennifer A., Smith, Albert Vernon, Warren, Helen R., Lin, Honghuang, Isaacs, Aaron, Liu, Ching Ti, Marten, Jonathan, Radmanesh, Farid, Hall, Leanne M., Grarup, Niels, Mei, Hao, Müller-Nurasyid, Martina, Huffman, Jennifer E., Verweij, Niek, Guo, Xiuqing, Yao, Jie, Li-Gao, Ruifang, van den Berg, Marten, Weiss, Stefan, Prins, Bram P., van Setten, Jessica, Haessler, Jeffrey, Lyytikäinen, Leo Pekka, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z., Bis, Joshua C., Austin, Tom, Chen, Yii Der Ida, Psaty, Bruce M., Harrris, Tamara B., Launer, Lenore J., Padmanabhan, Sandosh, Dominiczak, Anna, Huang, Paul L., Xie, Zhijun, Ellinor, Patrick T., Kors, Jan A., Campbell, Archie, Murray, Alison D., Nelson, Christopher P., Tobin, Martin D., Bork-Jensen, Jette, Hansen, Torben, Pedersen, Oluf, Linneberg, Allan, Sinner, Moritz F., Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Perz, Siegfried, Kolcic, Ivana, Rudan, Igor, de Boer, Rudolf A., van der Meer, Peter, Lin, Henry J., Taylor, Kent D., de Mutsert, Renée, Trompet, Stella, Jukema, J. Wouter, Maan, Arie C., Stricker, Bruno H.C., Rivadeneira, Fernando, Uitterlinden, André, Völker, Uwe, Homuth, Georg, Völzke, Henry, Felix, Stephan B., Mangino, Massimo, Spector, Timothy D., Bots, Michiel L., Perez, Marco, Raitakari, Olli T., Kähönen, Mika, Mononen, Nina, Gudnason, Vilmundur, Munroe, Patricia B., Lubitz, Steven A., van Duijn, Cornelia M., Newton-Cheh, Christopher H., Hayward, Caroline, Rosand, Jonathan, Samani, Nilesh J., Kanters, Jørgen K., Wilson, James G., Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R., Rotter, Jerome I., Mook-Kanamori, Dennis O., Eijgelsheim, Mark, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W., Kooperberg, Charles, Lehtimäki, Terho, Arking, Dan E., and Sotoodehnia, Nona
Published: 2018

43. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author: Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I.W., Groot, Mark C.H., Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans Jörgen, Grant, Struan F.A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M.M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L.R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng Hung, Lin, Li An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'An, Lubitz, Steven A., Lyytikäinen, Leo Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Olde Loohuis, Loes M., Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R.B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R.B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H.H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, Van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., Loos, Ruth J.F., Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I.W., Groot, Mark C.H., Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans Jörgen, Grant, Struan F.A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M.M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L.R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng Hung, Lin, Li An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'An, Lubitz, Steven A., Lyytikäinen, Leo Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Olde Loohuis, Loes M., Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R.B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R.B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H.H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, Van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., and Loos, Ruth J.F.
Published: 2018

44. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author: Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., Jamshidi, Yalda, Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., and Jamshidi, Yalda
Published: 2018

45. Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval

Author: Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, Isaacs, Aaron, Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, and Isaacs, Aaron
Published: 2018

46. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals

Author: Bihlmeyer, Nathan A., Brody, Jennifer A., Smith, Albert Vernon, Warren, Helen R., Lin, Honghuang, Isaacs, Aaron, Liu, Ching Ti, Marten, Jonathan, Radmanesh, Farid, Hall, Leanne M., Grarup, Niels, Mei, Hao, Müller-Nurasyid, Martina, Huffman, Jennifer E., Verweij, Niek, Guo, Xiuqing, Yao, Jie, Li-Gao, Ruifang, van den Berg, Marten, Weiss, Stefan, Prins, Bram P., van Setten, Jessica, Haessler, Jeffrey, Lyytikäinen, Leo Pekka, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z., Bis, Joshua C., Austin, Tom, Chen, Yii Der Ida, Psaty, Bruce M., Harrris, Tamara B., Launer, Lenore J., Padmanabhan, Sandosh, Dominiczak, Anna, Huang, Paul L., Xie, Zhijun, Ellinor, Patrick T., Kors, Jan A., Campbell, Archie, Murray, Alison D., Nelson, Christopher P., Tobin, Martin D., Bork-Jensen, Jette, Hansen, Torben, Pedersen, Oluf, Linneberg, Allan, Sinner, Moritz F., Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Perz, Siegfried, Kolcic, Ivana, Rudan, Igor, de Boer, Rudolf A., van der Meer, Peter, Lin, Henry J., Taylor, Kent D., de Mutsert, Renée, Trompet, Stella, Jukema, J. Wouter, Maan, Arie C., Stricker, Bruno H.C., Rivadeneira, Fernando, Uitterlinden, André, Völker, Uwe, Homuth, Georg, Völzke, Henry, Felix, Stephan B., Mangino, Massimo, Spector, Timothy D., Bots, Michiel L., Perez, Marco, Raitakari, Olli T., Kähönen, Mika, Mononen, Nina, Gudnason, Vilmundur, Munroe, Patricia B., Lubitz, Steven A., van Duijn, Cornelia M., Newton-Cheh, Christopher H., Hayward, Caroline, Rosand, Jonathan, Samani, Nilesh J., Kanters, Jørgen K., Wilson, James G., Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R., Rotter, Jerome I., Mook-Kanamori, Dennis O., Eijgelsheim, Mark, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W., Kooperberg, Charles, Lehtimäki, Terho, Arking, Dan E., Sotoodehnia, Nona, Bihlmeyer, Nathan A., Brody, Jennifer A., Smith, Albert Vernon, Warren, Helen R., Lin, Honghuang, Isaacs, Aaron, Liu, Ching Ti, Marten, Jonathan, Radmanesh, Farid, Hall, Leanne M., Grarup, Niels, Mei, Hao, Müller-Nurasyid, Martina, Huffman, Jennifer E., Verweij, Niek, Guo, Xiuqing, Yao, Jie, Li-Gao, Ruifang, van den Berg, Marten, Weiss, Stefan, Prins, Bram P., van Setten, Jessica, Haessler, Jeffrey, Lyytikäinen, Leo Pekka, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z., Bis, Joshua C., Austin, Tom, Chen, Yii Der Ida, Psaty, Bruce M., Harrris, Tamara B., Launer, Lenore J., Padmanabhan, Sandosh, Dominiczak, Anna, Huang, Paul L., Xie, Zhijun, Ellinor, Patrick T., Kors, Jan A., Campbell, Archie, Murray, Alison D., Nelson, Christopher P., Tobin, Martin D., Bork-Jensen, Jette, Hansen, Torben, Pedersen, Oluf, Linneberg, Allan, Sinner, Moritz F., Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Perz, Siegfried, Kolcic, Ivana, Rudan, Igor, de Boer, Rudolf A., van der Meer, Peter, Lin, Henry J., Taylor, Kent D., de Mutsert, Renée, Trompet, Stella, Jukema, J. Wouter, Maan, Arie C., Stricker, Bruno H.C., Rivadeneira, Fernando, Uitterlinden, André, Völker, Uwe, Homuth, Georg, Völzke, Henry, Felix, Stephan B., Mangino, Massimo, Spector, Timothy D., Bots, Michiel L., Perez, Marco, Raitakari, Olli T., Kähönen, Mika, Mononen, Nina, Gudnason, Vilmundur, Munroe, Patricia B., Lubitz, Steven A., van Duijn, Cornelia M., Newton-Cheh, Christopher H., Hayward, Caroline, Rosand, Jonathan, Samani, Nilesh J., Kanters, Jørgen K., Wilson, James G., Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R., Rotter, Jerome I., Mook-Kanamori, Dennis O., Eijgelsheim, Mark, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W., Kooperberg, Charles, Lehtimäki, Terho, Arking, Dan E., and Sotoodehnia, Nona
Published: 2018

47. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author: Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I.W., Groot, Mark C.H., Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans Jörgen, Grant, Struan F.A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M.M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L.R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng Hung, Lin, Li An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'An, Lubitz, Steven A., Lyytikäinen, Leo Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Olde Loohuis, Loes M., Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R.B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R.B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H.H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, Van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., Loos, Ruth J.F., Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G.D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C.Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I.W., Groot, Mark C.H., Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans Jörgen, Grant, Struan F.A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M.M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L.R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng Hung, Lin, Li An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'An, Lubitz, Steven A., Lyytikäinen, Leo Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Olde Loohuis, Loes M., Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R.B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R.B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H.H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, Van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., and Loos, Ruth J.F.
Published: 2018

48. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author: Turcot, Valerie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tonu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Goncalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Ines, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Joergen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Hakan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltan, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mannisto, Satu, Marenne, Gaelle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renstrom, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H. -H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Voelker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., Loos, Ruth J. F., Turcot, Valerie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tonu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Goncalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Ines, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Joergen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Hakan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltan, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mannisto, Satu, Marenne, Gaelle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renstrom, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H. -H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Voelker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., and Loos, Ruth J. F.
Abstract: Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
Published: 2018

49. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals

Author: Bihlmeyer, Nathan A., Brody, Jennifer A., Smith, Albert Vernon, Warren, Helen R., Lin, Honghuang, Isaacs, Aaron, Liu, Ching Ti, Marten, Jonathan, Radmanesh, Farid, Hall, Leanne M., Grarup, Niels, Mei, Hao, Müller-Nurasyid, Martina, Huffman, Jennifer E., Verweij, Niek, Guo, Xiuqing, Yao, Jie, Li-Gao, Ruifang, van den Berg, Marten, Weiss, Stefan, Prins, Bram P., van Setten, Jessica, Haessler, Jeffrey, Lyytikäinen, Leo Pekka, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z., Bis, Joshua C., Austin, Tom, Chen, Yii Der Ida, Psaty, Bruce M., Harrris, Tamara B., Launer, Lenore J., Padmanabhan, Sandosh, Dominiczak, Anna, Huang, Paul L., Xie, Zhijun, Ellinor, Patrick T., Kors, Jan A., Campbell, Archie, Murray, Alison D., Nelson, Christopher P., Tobin, Martin D., Bork-Jensen, Jette, Hansen, Torben, Pedersen, Oluf, Linneberg, Allan, Sinner, Moritz F., Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Perz, Siegfried, Kolcic, Ivana, Rudan, Igor, de Boer, Rudolf A., van der Meer, Peter, Lin, Henry J., Taylor, Kent D., de Mutsert, Renée, Trompet, Stella, Jukema, J. Wouter, Maan, Arie C., Stricker, Bruno H.C., Rivadeneira, Fernando, Uitterlinden, André, Völker, Uwe, Homuth, Georg, Völzke, Henry, Felix, Stephan B., Mangino, Massimo, Spector, Timothy D., Bots, Michiel L., Perez, Marco, Raitakari, Olli T., Kähönen, Mika, Mononen, Nina, Gudnason, Vilmundur, Munroe, Patricia B., Lubitz, Steven A., van Duijn, Cornelia M., Newton-Cheh, Christopher H., Hayward, Caroline, Rosand, Jonathan, Samani, Nilesh J., Kanters, Jørgen K., Wilson, James G., Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R., Rotter, Jerome I., Mook-Kanamori, Dennis O., Eijgelsheim, Mark, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W., Kooperberg, Charles, Lehtimäki, Terho, Arking, Dan E., Sotoodehnia, Nona, Bihlmeyer, Nathan A., Brody, Jennifer A., Smith, Albert Vernon, Warren, Helen R., Lin, Honghuang, Isaacs, Aaron, Liu, Ching Ti, Marten, Jonathan, Radmanesh, Farid, Hall, Leanne M., Grarup, Niels, Mei, Hao, Müller-Nurasyid, Martina, Huffman, Jennifer E., Verweij, Niek, Guo, Xiuqing, Yao, Jie, Li-Gao, Ruifang, van den Berg, Marten, Weiss, Stefan, Prins, Bram P., van Setten, Jessica, Haessler, Jeffrey, Lyytikäinen, Leo Pekka, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z., Bis, Joshua C., Austin, Tom, Chen, Yii Der Ida, Psaty, Bruce M., Harrris, Tamara B., Launer, Lenore J., Padmanabhan, Sandosh, Dominiczak, Anna, Huang, Paul L., Xie, Zhijun, Ellinor, Patrick T., Kors, Jan A., Campbell, Archie, Murray, Alison D., Nelson, Christopher P., Tobin, Martin D., Bork-Jensen, Jette, Hansen, Torben, Pedersen, Oluf, Linneberg, Allan, Sinner, Moritz F., Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Perz, Siegfried, Kolcic, Ivana, Rudan, Igor, de Boer, Rudolf A., van der Meer, Peter, Lin, Henry J., Taylor, Kent D., de Mutsert, Renée, Trompet, Stella, Jukema, J. Wouter, Maan, Arie C., Stricker, Bruno H.C., Rivadeneira, Fernando, Uitterlinden, André, Völker, Uwe, Homuth, Georg, Völzke, Henry, Felix, Stephan B., Mangino, Massimo, Spector, Timothy D., Bots, Michiel L., Perez, Marco, Raitakari, Olli T., Kähönen, Mika, Mononen, Nina, Gudnason, Vilmundur, Munroe, Patricia B., Lubitz, Steven A., van Duijn, Cornelia M., Newton-Cheh, Christopher H., Hayward, Caroline, Rosand, Jonathan, Samani, Nilesh J., Kanters, Jørgen K., Wilson, James G., Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R., Rotter, Jerome I., Mook-Kanamori, Dennis O., Eijgelsheim, Mark, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W., Kooperberg, Charles, Lehtimäki, Terho, Arking, Dan E., and Sotoodehnia, Nona
Published: 2018

50. Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval

Author: Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, Isaacs, Aaron, Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, and Isaacs, Aaron
Published: 2018

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Publication Year Range

Publication Type

Database

Publisher

103 results on '"Huang, Paul"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources