174 results on '"Rossin, Elizabeth J."'
Search Results
2. Central Retinal Artery Occlusion Following Sphenopalatine Artery Embolization: A Case Report and Review of the Literature
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Zhou, Henry W, Foulsham, William, and Rossin, Elizabeth J
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- 2024
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3. Targeting the Tie-2 Receptor With Faricimab in Central Serous Chorioretinopathy: A Case Series Motivated by a Genetic Finding
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Rämö, Joel T., Kim, Leo A., Stryjewski, Tomasz, Shah, Priya P., Bejjani, Romy, Brodie, Frank L., Eliott, Dean, Sobrin, Lucia, Vavvas, Demetrios G., and Rossin, Elizabeth J.
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- 2025
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4. Effectiveness of a telemedicine program for triage and diagnosis of emergent ophthalmic conditions
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Meshkin, Ryan S., Armstrong, Grayson W., Hall, Nathan E., Rossin, Elizabeth J., Hymowitz, Maggie B., and Lorch, Alice C.
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- 2023
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5. Multiethnic Genome-wide Association Study of Diabetic Retinopathy using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control
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Pollack, Samuela, Igo, Robert P, Jensen, Richard A, Christiansen, Mark, Li, Xiaohui, Cheng, Ching-Yu, Ng, Maggie CY, Smith, Albert V, Rossin, Elizabeth J, Segrè, Ayellet V, Davoudi, Samaneh, Tan, Gavin S, Chen, Yii-Der Ida, Kuo, Jane Z, Dimitrov, Latchezar M, Stanwyck, Lynn K, Meng, Weihua, Hosseini, S Mohsen, Imamura, Minako, Nousome, Darryl, Kim, Jihye, Hai, Yang, Jia, Yucheng, Ahn, Jeeyun, Leong, Aaron, Shah, Kaanan, Park, Kyu Hyung, Guo, Xiuqing, Ipp, Eli, Taylor, Kent D, Adler, Sharon G, Sedor, John R, Freedman, Barry I, Group, DCCT EDIC Research Group Family Investigation of Nephropathy and Diabetes-Eye Research, Lee, I-Te, Sheu, Wayne H-H, Kubo, Michiaki, Takahashi, Atsushi, Hadjadj, Samy, Marre, Michel, Tregouet, David-Alexandre, Mckean-Cowdin, Roberta, Varma, Rohit, McCarthy, Mark I, Groop, Leif, Ahlqvist, Emma, Lyssenko, Valeriya, Agardh, Elisabet, Morris, Andrew, Doney, Alex SF, Colhoun, Helen M, Toppila, Iiro, Sandholm, Niina, Groop, Per-Henrik, Maeda, Shiro, Hanis, Craig L, Penman, Alan, Chen, Ching J, Hancock, Heather, Mitchell, Paul, Craig, Jamie E, Chew, Emily Y, Paterson, Andrew D, Grassi, Michael A, Palmer, Colin, Bowden, Donald W, Yaspan, Brian L, Siscovick, David, Cotch, Mary Frances, Wang, Jie Jin, Burdon, Kathryn P, Wong, Tien Y, Klein, Barbara EK, Klein, Ronald, Rotter, Jerome I, Iyengar, Sudha K, Price, Alkes, and Sobrin, Lucia
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Biomedical and Clinical Sciences ,Genetics ,Human Genome ,Diabetes ,Prevention ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Good Health and Well Being ,Blood Glucose ,Diabetes Mellitus ,Type 2 ,Diabetic Retinopathy ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Glycated Hemoglobin ,Humans ,Meta-Analysis as Topic ,Polymorphism ,Single Nucleotide ,Protein Binding ,Family Investigation of Nephropathy and Diabetes-Eye Research Group ,DCCT/EDIC Research Group ,Medical and Health Sciences ,Endocrinology & Metabolism ,Biomedical and clinical sciences - Abstract
To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a P value
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- 2019
6. Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses
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Nathan, Anusha, Rossin, Elizabeth J., Kaseke, Clarety, Park, Ryan J., Khatri, Ashok, Koundakjian, Dylan, Urbach, Jonathan M., Singh, Nishant K., Bashirova, Arman, Tano-Menka, Rhoda, Senjobe, Fernando, Waring, Michael T., Piechocka-Trocha, Alicja, Garcia-Beltran, Wilfredo F., Iafrate, A. John, Naranbhai, Vivek, Carrington, Mary, Walker, Bruce D., and Gaiha, Gaurav D.
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- 2021
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7. Traumatic Retinal Detachment in Patients with Self-Injurious Behavior: An International Multicenter Study
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Rossin, Elizabeth J., Tsui, Irena, Wong, Sui Chien, Hou, Kirk K., Prakhunhungsit, Supalert, Blair, Michael P., Shapiro, Michael J., Leishman, Lisa, Nagiel, Aaron, Lifton, Jacob A., Quiram, Polly, Ringeisen, Alexander L., Henderson, Robert H., Arruti, Natalia, Buzzacco, Dominic M., Kusaka, Shunji, Ferrone, Philip J., Belin, Peter J., Chang, Emmanuel, Hubschman, Jean-Pierre, Murray, Timothy G., Leung, Ella H., Wu, Wei-Chi, Olsen, Karl R., Harper, C. Armitage, III, Rahmani, Safa, Goldstein, Jessica, Lee, Thomas, Nudleman, Eric, Cernichiaro-Espinosa, Linda A., Chhablani, Jay, Berrocal, Audina M., and Yonekawa, Yoshihiro
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- 2021
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8. HLA class-I-peptide stability mediates CD8+ T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV
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Kaseke, Clarety, Park, Ryan J., Singh, Nishant K., Koundakjian, Dylan, Bashirova, Arman, Garcia Beltran, Wilfredo F., Takou Mbah, Overbeck C., Ma, Jiaqi, Senjobe, Fernando, Urbach, Jonathan M., Nathan, Anusha, Rossin, Elizabeth J., Tano-Menka, Rhoda, Khatri, Ashok, Piechocka-Trocha, Alicja, Waring, Michael T., Birnbaum, Michael E., Baker, Brian M., Carrington, Mary, Walker, Bruce D., and Gaiha, Gaurav D.
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- 2021
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9. An mRNA-encoded dominant-negative inhibitor of transcription factor RUNX1 suppresses vitreoretinal disease in experimental models.
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O'Hare, Michael, Miller, William P., Arevalo-Alquichire, Said, Amarnani, Dhanesh, Apryani, Evhy, Perez-Corredor, Paula, Marino, Claudia, Shu, Daisy Y., Vanderleest, Timothy E., Muriel-Torres, Andres, Gordon, Harper B., Gunawan, Audrey L., Kaplan, Bryan A., Barake, Karim W., Bejjani, Romy P., Doan, Tri H., Lin, Rose, Delgado-Tirado, Santiago, Gonzalez-Buendia, Lucia, and Rossin, Elizabeth J.
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PRIMARY cell culture ,MACULAR degeneration ,PROLIFERATIVE vitreoretinopathy ,EPITHELIAL-mesenchymal transition ,RETINAL detachment ,RETINAL surgery - Abstract
Messenger RNA (mRNA)–based therapies are a promising approach to medical treatment. Except for infectious diseases, no other disease has mRNA-based therapies available. The eye is an ideal model for mRNA therapeutic development because it requires limited dosing. Proliferative vitreoretinopathy (PVR) is a blinding condition caused by retinal detachment that now lacks available medical treatment, with surgery as the only treatment option. We previously implicated runt-related transcription factor-1 (RUNX1) as a driver of epithelial-to-mesenchymal transition (EMT) in PVR and as a critical mediator of aberrant ocular angiogenesis when up-regulated. On the basis of these findings, an mRNA was designed to express a dominant-negative inhibitor of RUNX1 (RUNX1-Trap). We show that RUNX1-Trap delivered in polymer-lipidoid complexes or lipid nanoparticles sequestered RUNX1 in the cytosol and strongly reduced proliferation in primary cell cultures established from fibrotic membranes derived from patients with PVR. We assessed the preclinical efficacy of intraocular delivery of mRNA-encoded RUNX1-Trap in a rabbit model of PVR and in a laser-induced mouse model of aberrant angiogenesis often used to study wet age-related macular degeneration. mRNA-encoded RUNX1-Trap suppressed ocular pathology, measured as pathological scores in the rabbit PVR model and leakage and lesion size in the laser-induced choroidal neovascularization mouse model. mRNA-encoded RUNX1-Trap also strongly reduced proliferation in a human ex vivo explant model of PVR. These data demonstrate the therapeutic potential of mRNA-encoded therapeutic molecules with dominant-negative properties, highlighting the potential of mRNA-based therapies beyond standard gene supplementation approaches. Editor's summary: Proliferative vitreoretinopathy (PVR) is a complication after retinal detachment. It occurs when cells proliferate in the vitreous cavity, and surgery is now the only treatment option. Here, O'Hare and colleagues screened mRNA transcripts for potential therapeutic properties upon intracellular delivery and identified a dominant-negative inhibitor for RUNX1 (RUNX1-Trap). The transcription factor RUNX1 has been shown to promote PVR pathology by mediating epithelial-to-mesenchymal transition. Delivery of mRNA-encoded RUNX1-Trap inhibited proliferation of PVR cell models, ameliorated pathology in two in vivo models of retinal disease, and inhibited growth of patient-derived PVR explants. These data support further development of RUNX1-Trap for PVR. —Daniela Neuhofer [ABSTRACT FROM AUTHOR]
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- 2024
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10. Trends in Anti-Vascular Endothelial Growth Factor Original Medicare Part B Claims in the United States, 2014–2019.
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Desai, Sarishka, Sekimitsu, Sayuri, Rossin, Elizabeth J., and Zebardast, Nazlee
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MEDICARE Part B ,ENDOTHELIAL growth factors ,INTRAVITREAL injections ,DRUG accessibility ,MEDICARE costs ,RANIBIZUMAB - Abstract
Purpose: To characterize trends in use of and expenditure for the intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept, ranibizumab, and bevacizumab among the population enrolled in Original Medicare from 2014 to 2019. Methods: The Centers for Medicare and Medicaid Services Physician and Other Supplier Public Use File was used to extract Medicare Part B fee-for-service outpatient injection claims data submitted by ophthalmologists. Multivariable linear regression models were used to evaluate the association between reimbursement, ophthalmologist availability, and agent administration rate. Results: Between 2014 and 2019, 17,588,995 intravitreal injection claims were filed by 4218 US ophthalmologists. Medicare costs for anti-VEGF injections increased from 2.51 B USD in 2014 to 4.02 B USD in 2019. Increased state-level ophthalmologist availability and incremental increases in average reimbursement amounts were found to be significantly associated with a 6.8-fold variation in 2019 overall anti-VEGF injection rates across states. Conclusions: Medicare injection rates and costs for anti-VEGF injections have both increased between 2014 and 2019, largely driven by increased aflibercept use. There is a significant association between ophthalmologist availability and anti-VEGF injection rate on the state level, suggesting access to care may contribute to the observed state-level disparities in intravitreal injection rates. Further characterization of factors contributing to the state-level variation in injection rates of individual anti-VEGF agents may help inform interventions promoting equitable access to and use of these drugs. [ABSTRACT FROM AUTHOR]
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- 2024
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11. 52 Genetic Loci Influencing Myocardial Mass
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van der Harst, Pim, van Setten, Jessica, Verweij, Niek, Vogler, Georg, Franke, Lude, Maurano, Matthew T, Wang, Xinchen, Leach, Irene Mateo, Eijgelsheim, Mark, Sotoodehnia, Nona, Hayward, Caroline, Sorice, Rossella, Meirelles, Osorio, Lyytikäinen, Leo-Pekka, Polašek, Ozren, Tanaka, Toshiko, Arking, Dan E, Ulivi, Sheila, Trompet, Stella, Müller-Nurasyid, Martina, Smith, Albert V, Dörr, Marcus, Kerr, Kathleen F, Magnani, Jared W, Del Greco M., Fabiola, Zhang, Weihua, Nolte, Ilja M, Silva, Claudia T, Padmanabhan, Sandosh, Tragante, Vinicius, Esko, Tõnu, Abecasis, Gonçalo R, Adriaens, Michiel E, Andersen, Karl, Barnett, Phil, Bis, Joshua C, Bodmer, Rolf, Buckley, Brendan M, Campbell, Harry, Cannon, Megan V, Chakravarti, Aravinda, Chen, Lin Y, Delitala, Alessandro, Devereux, Richard B, Doevendans, Pieter A, Dominiczak, Anna F, Ferrucci, Luigi, Ford, Ian, Gieger, Christian, Harris, Tamara B, Haugen, Eric, Heinig, Matthias, Hernandez, Dena G, Hillege, Hans L, Hirschhorn, Joel N, Hofman, Albert, Hubner, Norbert, Hwang, Shih-Jen, Iorio, Annamaria, Kähönen, Mika, Kellis, Manolis, Kolcic, Ivana, Kooner, Ishminder K, Kooner, Jaspal S, Kors, Jan A, Lakatta, Edward G, Lage, Kasper, Launer, Lenore J, Levy, Daniel, Lundby, Alicia, Macfarlane, Peter W, May, Dalit, Meitinger, Thomas, Metspalu, Andres, Nappo, Stefania, Naitza, Silvia, Neph, Shane, Nord, Alex S, Nutile, Teresa, Okin, Peter M, Olsen, Jesper V, Oostra, Ben A, Penninger, Josef M, Pennacchio, Len A, Pers, Tune H, Perz, Siegfried, Peters, Annette, Pinto, Yigal M, Pfeufer, Arne, Pilia, Maria Grazia, Pramstaller, Peter P, Prins, Bram P, Raitakari, Olli T, Raychaudhuri, Soumya, Rice, Ken M, Rossin, Elizabeth J, Rotter, Jerome I, Schafer, Sebastian, Schlessinger, David, and Schmidt, Carsten O
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Medical Physiology ,Biomedical and Clinical Sciences ,Heart Disease - Coronary Heart Disease ,Human Genome ,Heart Disease ,Biotechnology ,Cardiovascular ,Genetics ,2.1 Biological and endogenous factors ,Animals ,Cardiomegaly ,Genetic Loci ,Genome-Wide Association Study ,Humans ,electrocardiogram ,genetic association study ,heart failure ,left ventricular hypertrophy ,QRS ,Cardiorespiratory Medicine and Haematology ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundMyocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.ObjectivesThis meta-analysis sought to gain insights into the genetic determinants of myocardial mass.MethodsWe carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.ResultsWe identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo.ConclusionsTaken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.
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- 2016
12. Structural topology defines protective CD8⁺ T cell epitopes in the HIV proteome
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Gaiha, Gaurav D., Rossin, Elizabeth J., Urbach, Jonathan, Landeros, Christian, Collins, David R., Nwonu, Chioma, Muzhingi, Itai, Anahtar, Melis N., Waring, Olivia M., Piechocka-Trocha, Alicja, Waring, Michael, Worrall, Daniel P., Ghebremichael, Musie S., Newman, Ruchi M., Power, Karen A., Allen, Todd M., Chodosh, James, and Walker, Bruce D.
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- 2019
13. Case 43: Large Zone III Open Globe from a Finger Injury While Playing Basketball
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Rossin, Elizabeth J., Chee, Yewlin E., Veldman, Peter B., Eliott, Dean, Grob, Seanna, editor, and Kloek, Carolyn, editor
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- 2018
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14. Open Globe Injuries From Garage Door Springs
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Shah, Priya P., primary, Bejjani, Romy, additional, Singhanetr, Panisa, additional, Patel, Neal S., additional, Patel, Nimesh A., additional, Armstrong, Grayson W., additional, and Rossin, Elizabeth J., additional
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- 2023
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15. Topical delivery of a small molecule RUNX1 transcription factor inhibitor for the treatment of proliferative vitreoretinopathy
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Delgado-Tirado, Santiago, Amarnani, Dhanesh, Zhao, Guannan, Rossin, Elizabeth J., Eliott, Dean, Miller, John B., Greene, Whitney A., Ramos, Leslie, Arevalo-Alquichire, Said, Leyton-Cifuentes, David, Gonzalez-Buendia, Lucia, Isaacs-Bernal, Daniela, Whitmore, Hannah A. B., Chmielewska, Natalia, Duffy, Brandon V., Kim, Eric, Wang, Heuy-Ching, Ruiz-Moreno, Jose M., Kim, Leo A., and Arboleda-Velasquez, Joseph F.
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- 2020
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16. Ophthalmic Trauma-Related Instruments-Critical Tools for Winning the Case.
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Sokol, Jared T. and Rossin, Elizabeth J.
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OCULAR injuries , *PROLIFERATIVE vitreoretinopathy , *SUTURING , *VITRECTOMY , *OPHTHALMIC surgery , *PROSTHETIC heart valves , *CORNEA injuries , *FOREIGN bodies , *CRYSTALLINE lens - Abstract
This document provides a comprehensive overview of the instruments and techniques used in ophthalmic surgery for trauma-related eye injuries. It emphasizes the importance of having a diverse toolkit and proper surgical exposure for successful outcomes. The article discusses the use of sutures, spatulas, and retractors for handling different parts of the eye during surgery. It also highlights the management of intraocular foreign body injuries, including the use of computed tomography for identification and various techniques for removal. The document concludes by listing essential instruments for open globe repair surgeries and emphasizes the need for further research in ophthalmic instrumentation to improve patient outcomes. [Extracted from the article]
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- 2024
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17. Site of Origin of the Ophthalmic Artery Influences the Risk for Retinal Versus Cerebral Embolic Events
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Rossin, Elizabeth J., Gilbert, Aubrey L., Koen, Nicholas, Leslie-Mazwi, Thabele M., Cunnane, Mary E., and Rizzo, Joseph F., III
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- 2020
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18. The Pleiotropy of Complement Factor H
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Rossin, Elizabeth J., primary and Sobrin, Lucia, additional
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- 2023
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19. Structure-based network analysis predicts mutations associated with inherited retinal disease
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Hauser, Blake M., primary, Luo, Yuyang, additional, Nathan, Anusha, additional, Gaiha, Gaurav D., additional, Vavvas, Demetrios, additional, Comander, Jason, additional, Pierce, Eric A., additional, Place, Emily M., additional, Bujakowska, Kinga M., additional, and Rossin, Elizabeth J., additional
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- 2023
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20. Reply
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Zekavat, Seyedeh Maryam, primary, Sekimitsu, Sayuri, additional, Doroodgar Jorshery, Saman, additional, Natarajan, Pradeep, additional, Rossin, Elizabeth J., additional, Del Priore, Lucian, additional, Zebardast, Nazlee, additional, and Wang, Jay C., additional
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- 2023
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21. Survey of variation in human transcription factors reveals prevalent DNA binding changes
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Barrera, Luis A., Vedenko, Anastasia, Kurland, Jesse V., Rogers, Julia M., Gisselbrecht, Stephen S., Rossin, Elizabeth J., Woodard, Jaie, Mariani, Luca, Kock, Kian Hong, Inukai, Sachi, Siggers, Trevor, Shokri, Leila, Gordân, Raluca, Sahni, Nidhi, Cotsapas, Chris, Hao, Tong, Yi, Song, Kellis, Manolis, Daly, Mark J., Vidal, Marc, Hill, David E., and Bulyk, Martha L.
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- 2016
22. Reevaluating the Risk of Serious Adverse Events of Carbonic Anhydrase Inhibitors
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Bleicher, Isaac D., primary, Rossin, Elizabeth J., additional, and Vavvas, Demetrios G., additional
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- 2022
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23. Bacillary Layer Detachment Associated With Endogenous Fungal Endophthalmitis
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Cox, Jacob T., primary, Wu, Frances, additional, Rossin, Elizabeth J., additional, Tang, William M., additional, and Eliott, Dean, additional
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- 2022
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24. SARS-CoV-2 RNA Detected in Vitreous Samples Obtained at Autopsy
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Tieger, Marisa, primary, Das Adhikari, Upasana, additional, Mukai, Shizuo, additional, Farcasnu, Mara, additional, Stone, James R., additional, Eliott, Dean, additional, Kim, Leo A., additional, Kwon, Douglas S., additional, and Rossin, Elizabeth J., additional
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- 2022
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25. sj-docx-1-vrd-10.1177_24741264221083408 – Supplemental material for SARS-CoV-2 RNA Detected in Vitreous Samples Obtained at Autopsy
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Tieger, Marisa, Das Adhikari, Upasana, Mukai, Shizuo, Farcasnu, Mara, Stone, James R., Eliott, Dean, Kim, Leo A., Kwon, Douglas S., and Rossin, Elizabeth J.
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FOS: Clinical medicine ,Medicine ,111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified - Abstract
Supplemental material, sj-docx-1-vrd-10.1177_24741264221083408 for SARS-CoV-2 RNA Detected in Vitreous Samples Obtained at Autopsy by Marisa Tieger, Upasana Das Adhikari, Shizuo Mukai, Mara Farcasnu, James R. Stone, Dean Eliott, Leo A. Kim, Douglas S. Kwon and Elizabeth J. Rossin in Journal of VitreoRetinal Diseases
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- 2022
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26. Hypopyon and White Cataract Due to an Intraocular Helminth
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Wai, Karen M., primary, Rossin, Elizabeth J., additional, Delgado-Tirado, Santiago, additional, Cadorette, James J., additional, Boody, Rick P., additional, Rodriguez, Marianeli, additional, and Kim, Leo A., additional
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- 2022
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27. Two Cases of Cutibacterium acnes ( C acnes ) Endophthalmitis Manifesting With Unusual Epiretinal Deposits
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Rossin, Elizabeth J., primary, Tieger, Marisa, additional, Rao, Narsing A., additional, O'Hearn, Thomas M., additional, Eliott, Dean, additional, and Wu, David M., additional
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- 2022
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28. Effectiveness of a telemedicine program for triage and diagnosis of emergent ophthalmic conditions
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Meshkin, Ryan S., primary, Armstrong, Grayson W., additional, Hall, Nathan E., additional, Rossin, Elizabeth J., additional, Hymowitz, Maggie B., additional, and Lorch, Alice C., additional
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- 2022
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29. PROTEIN EVOLUTION: Survey of variation in human transcription factors reveals prevalent DNA binding changes
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Barrera, Luis A., Vedenko, Anastasia, Kurland, Jesse V., Rogers, Julia M., Gisselbrecht, Stephen S., Rossin, Elizabeth J., Woodard, Jaie, Mariani, Luca, Kock, Kian Hong, Inukai, Sachi, Siggers, Trevor, Shokri, Leila, Gordăn, Raluca, Sahni, Nidhi, Cotsapas, Chris, Hao, Tong, Yi, Song, Kellis, Manolis, Daly, Mark J., Vidal, Marc, Hill, David E., and Bulyk, Martha L.
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- 2016
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30. Aflibercept for Retinopathy of Prematurity: A Systematic Review and Meta-Analysis
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Chen, Po-Yu (Jay), primary, Rossin, Elizabeth J., additional, and Vavvas, Demetrios G., additional
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- 2021
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31. Overlap of Genetic Loci for Central Serous Chorioretinopathy With Age-Related Macular Degeneration
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Rämö, Joel T., Abner, Erik, van Dijk, Elon H. C., Wang, Xin, Brinks, Joost, Nikopensius, Tiit, Nõukas, Margit, Marjonen, Heidi, Silander, Kaisa, Jukarainen, Sakari, Kiiskinen, Tuomo, Choi, Seung Hoan, Kajanne, Risto, Mehtonen, Juha, Palta, Priit, Lubitz, Steven A., Kaarniranta, Kai, Sobrin, Lucia, Kurki, Mitja, Yzer, Suzanne, Ellinor, Patrick T., Esko, Tõnu, Daly, Mark J., den Hollander, Anneke I., Palotie, Aarno, Turunen, Joni A., Boon, Camiel J. F., and Rossin, Elizabeth J.
- Abstract
IMPORTANCE: Central serous chorioretinopathy (CSC) is a serous maculopathy of unknown etiology. Two of 3 previously reported CSC genetic risk loci are also associated with AMD. Improved understanding of CSC genetics may broaden our understanding of this genetic overlap and unveil mechanisms in both diseases. OBJECTIVE: To identify novel genetic risk factors for CSC and compare genetic risk factors for CSC and AMD. DESIGN, SETTING, AND PARTICIPANTS: Using International Classification of Diseases, Ninth (ICD-9) and Tenth (ICD-10) Revision code-based inclusion and exclusion criteria, patients with CSC and controls were identified in both the FinnGen study and the Estonian Biobank (EstBB). Also included in a meta-analysis were previously reported patients with chronic CSC and controls. Data were analyzed from March 1 to September 31, 2022. MAIN OUTCOMES AND MEASURES: Genome-wide association studies (GWASs) were performed in the biobank-based cohorts followed by a meta-analysis of all cohorts. The expression of genes prioritized by the polygenic priority score and nearest-gene methods were assessed in cultured choroidal endothelial cells and public ocular single-cell RNA sequencing data sets. The predictive utility of polygenic scores (PGSs) for CSC and AMD were evaluated in the FinnGen study. RESULTS: A total of 1176 patients with CSC and 526 787 controls (312 162 female [59.3%]) were included in this analysis: 552 patients with CSC and 343 461 controls were identified in the FinnGen study, 103 patients with CSC and 178 573 controls were identified in the EstBB, and 521 patients with chronic CSC and 3577 controls were included in a meta-analysis. Two previously reported CSC risk loci were replicated (near CFH and GATA5) and 3 novel loci were identified (near CD34/46, NOTCH4, and PREX1). The CFH and NOTCH4 loci were associated with AMD but in the opposite direction. Prioritized genes showed increased expression in cultured choroidal endothelial cells compared with other genes in the loci (median [IQR] of log 2 [counts per million], 7.3 [0.6] vs 4.7 [3.7]; P = .004) and were differentially expressed in choroidal vascular endothelial cells in single-cell RNA sequencing data (mean [SD] fold change, 2.05 [0.38] compared with other cell types; P < 7.1 × 10−20). A PGS for AMD was predictive of reduced CSC risk (odds ratio, 0.76; 95% CI, 0.70-0.83 per +1 SD in AMD-PGS; P = 7.4 × 10−10). This association may have been mediated by loci containing complement genes. CONCLUSIONS AND RELEVANCE: In this 3-cohort genetic association study, 5 genetic risk loci for CSC were identified, highlighting a likely role for genes involved in choroidal vascular function and complement regulation. Results suggest that polygenic AMD risk was associated with reduced risk of CSC and that this genetic overlap was largely due to loci containing complement genes.
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- 2023
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32. HLA class-I-peptide stability mediates CD8+ T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV
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Koch Institute for Integrative Cancer Research at MIT, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Biology, Kaseke, Clarety, Park, Ryan J, Singh, Nishant K, Koundakjian, Dylan, Bashirova, Arman, Garcia Beltran, Wilfredo F, Takou Mbah, Overbeck C, Ma, Jiaqi, Senjobe, Fernando, Urbach, Jonathan M, Nathan, Anusha, Rossin, Elizabeth J, Tano-Menka, Rhoda, Khatri, Ashok, Piechocka-Trocha, Alicja, Waring, Michael T, Birnbaum, Michael E, Baker, Brian M, Carrington, Mary, Walker, Bruce D, Gaiha, Gaurav D, Koch Institute for Integrative Cancer Research at MIT, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Biology, Kaseke, Clarety, Park, Ryan J, Singh, Nishant K, Koundakjian, Dylan, Bashirova, Arman, Garcia Beltran, Wilfredo F, Takou Mbah, Overbeck C, Ma, Jiaqi, Senjobe, Fernando, Urbach, Jonathan M, Nathan, Anusha, Rossin, Elizabeth J, Tano-Menka, Rhoda, Khatri, Ashok, Piechocka-Trocha, Alicja, Waring, Michael T, Birnbaum, Michael E, Baker, Brian M, Carrington, Mary, Walker, Bruce D, and Gaiha, Gaurav D
- Abstract
Defining factors that govern CD8+ T cell immunodominance is critical for the rational design of vaccines for viral pathogens. Here, we assess the contribution of human leukocyte antigen (HLA) class-I-peptide stability for 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with antigen processing (TAP)-deficient mono-allelic HLA-expressing cell lines. We find that immunodominant HIV epitopes increase surface stabilization of HLA class-I molecules in comparison to subdominant epitopes. HLA class-I-peptide stability is also strongly correlated with overall immunodominance hierarchies, particularly for epitopes from high-abundance proteins (e.g., Gag). Moreover, HLA alleles associated with HIV protection are preferentially stabilized by epitopes derived from topologically important viral regions at a greater frequency than neutral and risk alleles. These findings indicate that relative stabilization of HLA class-I is a key factor for CD8+ T cell epitope immunodominance hierarchies, with implications for HIV control and the design of T-cell-based vaccines.
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- 2021
33. Single-cell RNA sequencing: An overview for the ophthalmologist
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Rossin, Elizabeth J., primary, Sobrin, Lucia, additional, and Kim, Leo A., additional
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- 2021
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34. Factors Associated With Increased Risk of Serious Ocular Injury in the Setting of Orbital Fracture
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Rossin, Elizabeth J., primary, Szypko, Colleen, additional, Giese, Isaiah, additional, Hall, Nathan, additional, Gardiner, Matthew F., additional, and Lorch, Alice, additional
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- 2021
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35. Bilateral Hemorrhages in a Premature Infant With Subarachnoid Hemorrhage: An Underrecognized Etiology
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Rossin, Elizabeth J., primary and Vavvas, Demetrios G., additional
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- 2020
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36. Erratum. Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control. Diabetes 2019;68:441—456
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Pollack, Samuela, primary, Igo, Robert P., additional, Jensen, Richard A., additional, Christiansen, Mark, additional, Li, Xiaohui, additional, Cheng, Ching-Yu, additional, Ng, Maggie C.Y., additional, Smith, Albert V., additional, Rossin, Elizabeth J., additional, Segrè, Ayellet V., additional, Davoudi, Samaneh, additional, Tan, Gavin S., additional, Ida Chen, Yii-Der, additional, Kuo, Jane Z., additional, Dimitrov, Latchezar M., additional, Stanwyck, Lynn K., additional, Meng, Weihua, additional, Hosseini, S. Mohsen, additional, Imamura, Minako, additional, Nousome, Darryl, additional, Kim, Jihye, additional, Hai, Yang, additional, Jia, Yucheng, additional, Ahn, Jeeyun, additional, Leong, Aaron, additional, Shah, Kaanan, additional, Park, Kyu Hyung, additional, Guo, Xiuqing, additional, Ipp, Eli, additional, Taylor, Kent D., additional, Adler, Sharon G., additional, Sedor, John R., additional, Freedman, Barry I., additional, Lee, I-Te, additional, Sheu, Wayne H.-H., additional, Kubo, Michiaki, additional, Takahashi, Atsushi, additional, Hadjadj, Samy, additional, Marre, Michel, additional, Tregouet, David-Alexandre, additional, Mckean-Cowdin, Roberta, additional, Varma, Rohit, additional, McCarthy, Mark I., additional, Groop, Leif, additional, Ahlqvist, Emma, additional, Lyssenko, Valeriya, additional, Agardh, Elisabet, additional, Morris, Andrew, additional, Doney, Alex S.F., additional, Colhoun, Helen M., additional, Toppila, Iiro, additional, Sandholm, Niina, additional, Groop, Per-Henrik, additional, Maeda, Shiro, additional, Hanis, Craig L., additional, Penman, Alan, additional, Chen, Ching J., additional, Hancock, Heather, additional, Mitchell, Paul, additional, Craig, Jamie E., additional, Chew, Emily Y., additional, Paterson, Andrew D., additional, Grassi, Michael A., additional, Palmer, Colin, additional, Bowden, Donald W., additional, Yaspan, Brian L., additional, Siscovick, David, additional, Cotch, Mary Frances, additional, Wang, Jie Jin, additional, Burdon, Kathryn P., additional, Wong, Tien Y., additional, Klein, Barbara E.K., additional, Klein, Ronald, additional, Rotter, Jerome I., additional, Iyengar, Sudha K., additional, Price, Alkes L., additional, and Sobrin, Lucia, additional
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- 2020
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37. Two Cases of ( ) Endophthalmitis Manifesting With Unusual Epiretinal Deposits.
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Rossin, Elizabeth J., Tieger, Marisa, Rao, Narsing A., O'Hearn, Thomas M., Eliott, Dean, and Wu, David M.
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- 2022
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38. Structural topology defines protective CD8 + T cell epitopes in the HIV proteome
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Gaiha, Gaurav D., primary, Rossin, Elizabeth J., additional, Urbach, Jonathan, additional, Landeros, Christian, additional, Collins, David R., additional, Nwonu, Chioma, additional, Muzhingi, Itai, additional, Anahtar, Melis N., additional, Waring, Olivia M., additional, Piechocka-Trocha, Alicja, additional, Waring, Michael, additional, Worrall, Daniel P., additional, Ghebremichael, Musie S., additional, Newman, Ruchi M., additional, Power, Karen A., additional, Allen, Todd M., additional, Chodosh, James, additional, and Walker, Bruce D., additional
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- 2019
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39. Site of Origin of the Ophthalmic Artery Influences the Risk for Retinal Versus Cerebral Embolic Events.
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Rossin, Elizabeth J., Gilbert, Aubrey L., Koen, Nicholas, Leslie-Mazwi, Thabele M., Cunnane, Mary E., and Rizzo III, Joseph F.
- Abstract
Background: Embolic events leading to retinal ischemia or cerebral ischemia share common risk factors; however, it has been well documented that the rate of concurrent cerebral infarction is higher in patients with a history of transient ischemic attack (TIA) than in those with monocular vision loss (MVL) due to retinal ischemia. Despite the fact that emboli to the ophthalmic artery (OA) and middle cerebral artery share the internal carotid artery (ICA) as a common origin or transit for emboli, the asymmetry in their final destination has not been fully explained. We hypothesize that the anatomic location of the OA takeoff from the ICA may contribute to the differential flow of small emboli to the retinal circulation vs the cerebral circulation. Methods: We report a retrospective, comparative, case– control study on 28 patients with retinal ischemia and 26 patients with TIA or cerebral infarction caused by embolic events. All subjects underwent either computed tomography angiography or MRA. The location of the ipsilateral OA origin off the ICA was then graded in a blinded fashion and compared between cohorts. Vascular risk factors were collected for all patients, including age, sex, hypertension, hyperlipidemia, arrhythmia, diabetes, coronary artery disease, and smoking. Results: We find that in patients with retinal ischemia of embolic etiology, the ipsilateral OA takeoff from the ICA is more proximal than in patients with cerebral infarcts or TIA (P = 0.0002). We found no statistically significant differences in demographic, vascular, or systemic risk factors. Conclusions: We find that the mean anatomical location of the OA takeoff from the ICA is significantly more proximal in patients with MVL due to retinal ischemia compared with patients with TIA or cerebral ischemia. This finding contributes significantly to our understanding of a long observed but poorly understood phenomenon that patients with MVL are less likely to have concurrent cerebral ischemia than are patients with TIA. [ABSTRACT FROM AUTHOR]
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- 2021
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40. Bilateral Immediate Sequential Vitrectomy and Lensectomy for Bilateral Lens Dislocation in Severe Neonatal Marfan Syndrome
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Rossin, Elizabeth J., primary, VanderVeen, Deborah K., additional, and Yonekawa, Yoshihiro, additional
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- 2018
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41. Anterior–Posterior Persistent Fetal Vasculature With Multiple Stalks: Persistent Vasa Hyaloidea Propria
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Rossin, Elizabeth J., primary, VanderVeen, Deborah K., additional, and Yonekawa, Yoshihiro, additional
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- 2018
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42. 52 Genetic Loci Influencing Myocardial Mass
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Broad Institute of MIT and Harvard, Raychaudhuri, Soumya, van der Harst, Pim, van Setten, Jessica, Verweij, Niek, Vogler, Georg, Franke, Lude, Maurano, Matthew T., Wang, Xinchen, Mateo Leach, Irene, Eijgelsheim, Mark, Sotoodehnia, Nona, Hayward, Caroline, Sorice, Rossella, Meirelles, Osorio, Lyytikäinen, Leo-Pekka, Polašek, Ozren, Tanaka, Toshiko, Arking, Dan E., Ulivi, Sheila, Trompet, Stella, Müller-Nurasyid, Martina, Smith, Albert V., Dörr, Marcus, Kerr, Kathleen F., Magnani, Jared W., Fabiola Del Greco, M., Zhang, Weihua, Nolte, Ilja M., Silva, Claudia T., Padmanabhan, Sandosh, Tragante, Vinicius, Esko, Tõnu, Abecasis, Gonçalo R., Adriaens, Michiel E., Andersen, Karl, Barnett, Phil, Bis, Joshua C., Bodmer, Rolf, Buckley, Brendan M., Campbell, Harry, Cannon, Megan V., Chakravarti, Aravinda, Chen, Lin Y., Delitala, Alessandro, Devereux, Richard B., Doevendans, Pieter A., Dominiczak, Anna F., Ferrucci, Luigi, Ford, Ian, Gieger, Christian, Harris, Tamara B., Haugen, Eric, Heinig, Matthias, Hernandez, Dena G., Hillege, Hans L., Hirschhorn, Joel N., Hofman, Albert, Hubner, Norbert, Hwang, Shih-Jen, Iorio, Annamaria, Kahonen, Mika, Kellis, Manolis, Kolcic, Ivana, Kooner, Ishminder K., Kooner, Jaspal S., Kors, Jan A., Lakatta, Edward G., Lage, Kasper, Launer, Lenore J., Levy, Daniel, Lundby, Alicia, Macfarlane, Peter W., May, Dalit, Meitinger, Thomas, Metspalu, Andres, Nappo, Stefania, Naitza, Silvia, Neph, Shane, Nord, Alex S., Nutile, Teresa, Okin, Peter M., Olsen, Jesper V., Oostra, Ben A., Penninger, Josef M., Pennacchio, Len A., Pers, Tune H., Perz, Siegfried, Peters, Annette, Pinto, Yigal M., Pfeufer, Arne, Pilia, Maria Grazia, Pramstaller, Peter P., Prins, Bram P., Raitakari, Olli T., Rice, Ken M., Rossin, Elizabeth J., Rotter, Jerome I., Schafer, Sebastian, Schlessinger, David, Schmidt, Carsten O., Sehmi, Jobanpreet, Silljé, Herman H.W., Sinagra, Gianfranco, Sinner, Moritz F., Slowikowski, Kamil, Soliman, Elsayed Z., Spector, Timothy D., Spiering, Wilko, Stamatoyannopoulos, John A., Stolk, Ronald P., Strauch, Konstantin, Tan, Sian-Tsung, Tarasov, Kirill V., Trinh, Bosco, Uitterlinden, Andre G., van den Boogaard, Malou, van Duijn, Cornelia M., van Gilst, Wiek H., Viikari, Jorma S., Visscher, Peter M., Vitart, Veronique, Völker, Uwe, Waldenberger, Melanie, Weichenberger, Christian X., Westra, Harm-Jan, Wijmenga, Cisca, Wolffenbuttel, Bruce H., Yang, Jian, Bezzina, Connie R., Munroe, Patricia B., Snieder, Harold, Wright, Alan F., Rudan, Igor, Boyer, Laurie A., Asselbergs, Folkert W., van Veldhuisen, Dirk J., Stricker, Bruno H., Psaty, Bruce M., Ciullo, Marina, Sanna, Serena, Lehtimäki, Terho, Wilson, James F., Bandinelli, Stefania, Alonso, Alvaro, Gasparini, Paolo, Jukema, J. Wouter, Kääb, Stefan, Gudnason, Vilmundur, Felix, Stephan B., Heckbert, Susan R., de Boer, Rudolf A., Newton-Cheh, Christopher, Hicks, Andrew A., Chambers, John C., Jamshidi, Yalda, Visel, Axel, Christoffels, Vincent M., Isaacs, Aaron, Samani, Nilesh J., de Bakker, Paul I.W., Broad Institute of MIT and Harvard, Raychaudhuri, Soumya, van der Harst, Pim, van Setten, Jessica, Verweij, Niek, Vogler, Georg, Franke, Lude, Maurano, Matthew T., Wang, Xinchen, Mateo Leach, Irene, Eijgelsheim, Mark, Sotoodehnia, Nona, Hayward, Caroline, Sorice, Rossella, Meirelles, Osorio, Lyytikäinen, Leo-Pekka, Polašek, Ozren, Tanaka, Toshiko, Arking, Dan E., Ulivi, Sheila, Trompet, Stella, Müller-Nurasyid, Martina, Smith, Albert V., Dörr, Marcus, Kerr, Kathleen F., Magnani, Jared W., Fabiola Del Greco, M., Zhang, Weihua, Nolte, Ilja M., Silva, Claudia T., Padmanabhan, Sandosh, Tragante, Vinicius, Esko, Tõnu, Abecasis, Gonçalo R., Adriaens, Michiel E., Andersen, Karl, Barnett, Phil, Bis, Joshua C., Bodmer, Rolf, Buckley, Brendan M., Campbell, Harry, Cannon, Megan V., Chakravarti, Aravinda, Chen, Lin Y., Delitala, Alessandro, Devereux, Richard B., Doevendans, Pieter A., Dominiczak, Anna F., Ferrucci, Luigi, Ford, Ian, Gieger, Christian, Harris, Tamara B., Haugen, Eric, Heinig, Matthias, Hernandez, Dena G., Hillege, Hans L., Hirschhorn, Joel N., Hofman, Albert, Hubner, Norbert, Hwang, Shih-Jen, Iorio, Annamaria, Kahonen, Mika, Kellis, Manolis, Kolcic, Ivana, Kooner, Ishminder K., Kooner, Jaspal S., Kors, Jan A., Lakatta, Edward G., Lage, Kasper, Launer, Lenore J., Levy, Daniel, Lundby, Alicia, Macfarlane, Peter W., May, Dalit, Meitinger, Thomas, Metspalu, Andres, Nappo, Stefania, Naitza, Silvia, Neph, Shane, Nord, Alex S., Nutile, Teresa, Okin, Peter M., Olsen, Jesper V., Oostra, Ben A., Penninger, Josef M., Pennacchio, Len A., Pers, Tune H., Perz, Siegfried, Peters, Annette, Pinto, Yigal M., Pfeufer, Arne, Pilia, Maria Grazia, Pramstaller, Peter P., Prins, Bram P., Raitakari, Olli T., Rice, Ken M., Rossin, Elizabeth J., Rotter, Jerome I., Schafer, Sebastian, Schlessinger, David, Schmidt, Carsten O., Sehmi, Jobanpreet, Silljé, Herman H.W., Sinagra, Gianfranco, Sinner, Moritz F., Slowikowski, Kamil, Soliman, Elsayed Z., Spector, Timothy D., Spiering, Wilko, Stamatoyannopoulos, John A., Stolk, Ronald P., Strauch, Konstantin, Tan, Sian-Tsung, Tarasov, Kirill V., Trinh, Bosco, Uitterlinden, Andre G., van den Boogaard, Malou, van Duijn, Cornelia M., van Gilst, Wiek H., Viikari, Jorma S., Visscher, Peter M., Vitart, Veronique, Völker, Uwe, Waldenberger, Melanie, Weichenberger, Christian X., Westra, Harm-Jan, Wijmenga, Cisca, Wolffenbuttel, Bruce H., Yang, Jian, Bezzina, Connie R., Munroe, Patricia B., Snieder, Harold, Wright, Alan F., Rudan, Igor, Boyer, Laurie A., Asselbergs, Folkert W., van Veldhuisen, Dirk J., Stricker, Bruno H., Psaty, Bruce M., Ciullo, Marina, Sanna, Serena, Lehtimäki, Terho, Wilson, James F., Bandinelli, Stefania, Alonso, Alvaro, Gasparini, Paolo, Jukema, J. Wouter, Kääb, Stefan, Gudnason, Vilmundur, Felix, Stephan B., Heckbert, Susan R., de Boer, Rudolf A., Newton-Cheh, Christopher, Hicks, Andrew A., Chambers, John C., Jamshidi, Yalda, Visel, Axel, Christoffels, Vincent M., Isaacs, Aaron, Samani, Nilesh J., and de Bakker, Paul I.W.
- Abstract
Background Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. Objectives This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. Methods We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. Results We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10−8. These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. Conclusions Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.
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- 2017
43. CRISPR-based Gene Editing: A Guide for the Clinician
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Rossin, Elizabeth J., primary and Wu, David M., additional
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- 2017
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44. 52 Genetic Loci Influencing Myocardial Mass
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Experimentele Afd. Cardiologie 1, CMM Sectie Genomics and Bioinformatics, Circulatory Health, Cardiologie, Regenerative Medicine and Stem Cells, MS Interne Geneeskunde, CMM Groep Kaaij, Brain, Infection & Immunity, van der Harst, Pim, van Setten, Jessica, Verweij, Niek, Vogler, Georg, Franke, Lude, Maurano, Matthew T, Wang, Xinchen, Mateo Leach, Irene, Eijgelsheim, Mark, Sotoodehnia, Nona, Hayward, Caroline, Sorice, Rossella, Meirelles, Osorio, Lyytikäinen, Leo-Pekka, Polašek, Ozren, Tanaka, Toshiko, Arking, Dan E, Ulivi, Sheila, Trompet, Stella, Müller-Nurasyid, Martina, Smith, Albert V, Dörr, Marcus, Kerr, Kathleen F, Magnani, Jared W, Del Greco M, Fabiola, Zhang, Weihua, Nolte, Ilja M, Silva, Claudia T, Padmanabhan, Sandosh, Tragante Do O, V, Esko, Tõnu, Abecasis, Gonçalo R, Adriaens, Michiel E, Andersen, Karl, Barnett, Phil, Bis, Joshua C, Bodmer, Rolf, Buckley, Brendan M, Campbell, Harry, Cannon, Megan V, Chakravarti, Aravinda, Chen, Lin Y, Delitala, Alessandro, Devereux, Richard B, Doevendans, Pieter A, Dominiczak, Anna F, Ferrucci, Luigi, Ford, Ian, Gieger, Christian, Harris, Tamara B, Haugen, Eric, Heinig, Matthias, Hernandez, Dena G, Hillege, Hans L, Hirschhorn, Joel N, Hofman, Albert, Hubner, Norbert, Hwang, Shih-Jen, Iorio, Annamaria, Kähönen, Mika, Kellis, Manolis, Kolcic, Ivana, Kooner, Ishminder K, Kooner, Jaspal S, Kors, Jan A, Lakatta, Edward G, Lage, Kasper, Launer, Lenore J, Levy, Daniel, Lundby, Alicia, Macfarlane, Peter W, May, Dalit, Meitinger, Thomas, Metspalu, Andres, Nappo, Stefania, Naitza, Silvia, Neph, Shane, Nord, Alex S, Nutile, Teresa, Okin, Peter M, Olsen, Jesper V, Oostra, Ben A, Penninger, Josef M, Pennacchio, Len A, Pers, Tune H, Perz, Siegfried, Peters, Annette, Pinto, Yigal M, Pfeufer, Arne, Pilia, Maria Grazia, Pramstaller, Peter P, Prins, Bram P, Raitakari, Olli T, Raychaudhuri, Soumya, Rice, Ken M, Rossin, Elizabeth J, Rotter, Jerome I, Schafer, Sebastian, Schlessinger, David, Schmidt, Carsten O, Sehmi, Jobanpreet, Silljé, Herman H W, Sinagra, Gianfranco, Sinner, Moritz F, Slowikowski, Kamil, Soliman, Elsayed Z, Spector, Timothy D, Spiering, Wilko, Stamatoyannopoulos, John A, Stolk, Ronald P, Strauch, Konstantin, Tan, Sian-Tsung, Tarasov, Kirill V, Trinh, Bosco, Uitterlinden, Andre G, van den Boogaard, Malou, van Duijn, Cornelia M, van Gilst, Wiek H, Viikari, Jorma S, Visscher, Peter M, Vitart, Veronique, Völker, Uwe, Waldenberger, Melanie, Weichenberger, Christian X, Westra, Harm-Jan, Wijmenga, Cisca, Wolffenbuttel, Bruce H, Yang, Jian, Bezzina, Connie R, Munroe, Patricia B, Snieder, Harold, Wright, Alan F, Rudan, Igor, Boyer, Laurie A, Asselbergs, Folkert W, van Veldhuisen, Dirk J, Stricker, Bruno H, Psaty, Bruce M, Ciullo, Marina, Sanna, Serena, Lehtimäki, Terho, Wilson, James F, Bandinelli, Stefania, Alonso, Alvaro, Gasparini, Paolo, Jukema, J Wouter, Kääb, Stefan, Gudnason, Vilmundur, Felix, Stephan B, Heckbert, Susan R, de Boer, Rudolf A, Newton-Cheh, Christopher, Hicks, Andrew A, Chambers, John C, Jamshidi, Yalda, Visel, Axel, Christoffels, Vincent M, Isaacs, Aaron, Samani, Nilesh J, de Bakker, Paul I W, Experimentele Afd. Cardiologie 1, CMM Sectie Genomics and Bioinformatics, Circulatory Health, Cardiologie, Regenerative Medicine and Stem Cells, MS Interne Geneeskunde, CMM Groep Kaaij, Brain, Infection & Immunity, van der Harst, Pim, van Setten, Jessica, Verweij, Niek, Vogler, Georg, Franke, Lude, Maurano, Matthew T, Wang, Xinchen, Mateo Leach, Irene, Eijgelsheim, Mark, Sotoodehnia, Nona, Hayward, Caroline, Sorice, Rossella, Meirelles, Osorio, Lyytikäinen, Leo-Pekka, Polašek, Ozren, Tanaka, Toshiko, Arking, Dan E, Ulivi, Sheila, Trompet, Stella, Müller-Nurasyid, Martina, Smith, Albert V, Dörr, Marcus, Kerr, Kathleen F, Magnani, Jared W, Del Greco M, Fabiola, Zhang, Weihua, Nolte, Ilja M, Silva, Claudia T, Padmanabhan, Sandosh, Tragante Do O, V, Esko, Tõnu, Abecasis, Gonçalo R, Adriaens, Michiel E, Andersen, Karl, Barnett, Phil, Bis, Joshua C, Bodmer, Rolf, Buckley, Brendan M, Campbell, Harry, Cannon, Megan V, Chakravarti, Aravinda, Chen, Lin Y, Delitala, Alessandro, Devereux, Richard B, Doevendans, Pieter A, Dominiczak, Anna F, Ferrucci, Luigi, Ford, Ian, Gieger, Christian, Harris, Tamara B, Haugen, Eric, Heinig, Matthias, Hernandez, Dena G, Hillege, Hans L, Hirschhorn, Joel N, Hofman, Albert, Hubner, Norbert, Hwang, Shih-Jen, Iorio, Annamaria, Kähönen, Mika, Kellis, Manolis, Kolcic, Ivana, Kooner, Ishminder K, Kooner, Jaspal S, Kors, Jan A, Lakatta, Edward G, Lage, Kasper, Launer, Lenore J, Levy, Daniel, Lundby, Alicia, Macfarlane, Peter W, May, Dalit, Meitinger, Thomas, Metspalu, Andres, Nappo, Stefania, Naitza, Silvia, Neph, Shane, Nord, Alex S, Nutile, Teresa, Okin, Peter M, Olsen, Jesper V, Oostra, Ben A, Penninger, Josef M, Pennacchio, Len A, Pers, Tune H, Perz, Siegfried, Peters, Annette, Pinto, Yigal M, Pfeufer, Arne, Pilia, Maria Grazia, Pramstaller, Peter P, Prins, Bram P, Raitakari, Olli T, Raychaudhuri, Soumya, Rice, Ken M, Rossin, Elizabeth J, Rotter, Jerome I, Schafer, Sebastian, Schlessinger, David, Schmidt, Carsten O, Sehmi, Jobanpreet, Silljé, Herman H W, Sinagra, Gianfranco, Sinner, Moritz F, Slowikowski, Kamil, Soliman, Elsayed Z, Spector, Timothy D, Spiering, Wilko, Stamatoyannopoulos, John A, Stolk, Ronald P, Strauch, Konstantin, Tan, Sian-Tsung, Tarasov, Kirill V, Trinh, Bosco, Uitterlinden, Andre G, van den Boogaard, Malou, van Duijn, Cornelia M, van Gilst, Wiek H, Viikari, Jorma S, Visscher, Peter M, Vitart, Veronique, Völker, Uwe, Waldenberger, Melanie, Weichenberger, Christian X, Westra, Harm-Jan, Wijmenga, Cisca, Wolffenbuttel, Bruce H, Yang, Jian, Bezzina, Connie R, Munroe, Patricia B, Snieder, Harold, Wright, Alan F, Rudan, Igor, Boyer, Laurie A, Asselbergs, Folkert W, van Veldhuisen, Dirk J, Stricker, Bruno H, Psaty, Bruce M, Ciullo, Marina, Sanna, Serena, Lehtimäki, Terho, Wilson, James F, Bandinelli, Stefania, Alonso, Alvaro, Gasparini, Paolo, Jukema, J Wouter, Kääb, Stefan, Gudnason, Vilmundur, Felix, Stephan B, Heckbert, Susan R, de Boer, Rudolf A, Newton-Cheh, Christopher, Hicks, Andrew A, Chambers, John C, Jamshidi, Yalda, Visel, Axel, Christoffels, Vincent M, Isaacs, Aaron, Samani, Nilesh J, and de Bakker, Paul I W
- Published
- 2016
45. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
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Arking, Dan E, Pulit, Sara L, Crotti, Lia, van der Harst, Pim, Munroe, Patricia B, Koopmann, Tamara T, Sotoodehnia, Nona, Rossin, Elizabeth J, Morley, Michael, Wang, Xinchen, Johnson, Andrew D, Lundby, Alicia, Gudbjartsson, Daníel F, Noseworthy, Peter A, Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V, Dörr, Marcus, Müller-Nurasyid, Martina, Lahtinen, Annukka M, Nolte, Ilja M, Smith, Albert Vernon, Bis, Joshua C, Isaacs, Aaron, Newhouse, Stephen J, Evans, Daniel S, Post, Wendy S, Waggott, Daryl, Lyytikäinen, Leo-Pekka, Hicks, Andrew A, Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J, Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W, Naluai, Asa T, Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G, Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A, Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D, Harris, Tamara B, Launer, Lenore J, Shuldiner, Alan R, Alonso, Alvaro, Bader, Joel S, Ehret, Georg, Huang, Hailiang, Kao, W H Linda, Strait, James B, Macfarlane, Peter W, Brown, Morris, Caulfield, Mark J, Samani, Nilesh J, Kronenberg, Florian, Willeit, Johann, Smith, J Gustav, Greiser, Karin H, Meyer Zu Schwabedissen, Henriette, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R, Psaty, Bruce M, Rotter, Jerome I, Kolcic, Ivana, Polašek, Ozren, Wright, Alan F, Griffin, Maura, Daly, Mark J, Arnar, David O, Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C, Roden, Dan M, Zuvich, Rebecca L, Emilsson, Valur, Plump, Andrew S, Larson, Martin G, O'Donnell, Christopher J, Yin, Xiaoyan, Bobbo, Marco, D'Adamo, Adamo P, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R, Nalls, Michael A, Jula, Antti, Kontula, Kimmo K, Marjamaa, Annukka, Oikarinen, Lasse, Perola, Markus, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl-Heinz, Kälsch, Hagen, Nöthen, Markus M, den Hoed, Marcel, Loos, Ruth J F, Thelle, Dag S, Gieger, Christian, Meitinger, Thomas, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F, Waldenberger, Melanie, de Boer, Rudolf A, Franke, Lude, van der Vleuten, Pieter A, Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A M, Behr, Elijah R, Dalageorgou, Chrysoula, Giudicessi, John R, Medeiros-Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M, Scherer, Stephen W, Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E, Greco M, Fabiola Del, Fuchsberger, Christian, O'Connell, Jeffrey R, Lee, Wai K, Watt, Graham C M, Campbell, Harry, Wild, Sarah H, El Mokhtari, Nour E, Frey, Norbert, Asselbergs, Folkert W, Mateo Leach, Irene, Navis, Gerjan, van den Berg, Maarten P, van Veldhuisen, Dirk J, Kellis, Manolis, Krijthe, Bouwe P, Franco, Oscar H, Hofman, Albert, Kors, Jan A, Uitterlinden, André G, Witteman, Jacqueline C M, Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A, Abecasis, Gonçalo R, Lakatta, Edward G, Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R P, Völker, Uwe, Snieder, Harold, Spector, Timothy D, Ärnlöv, Johan, Lind, Lars, Sundström, Johan, Syvänen, Ann-Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T, Viikari, Jorma S, Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N, Paulweber, Bernhard, Haerting, Johannes, Dominiczak, Anna F, Nyberg, Fredrik, Whincup, Peter H, Hingorani, Aroon D, Schott, Jean-Jacques, Bezzina, Connie R, Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F, Rudan, Igor, Franke, Andre, Mühleisen, Thomas W, Pramstaller, Peter P, Lehtimäki, Terho J, Paterson, Andrew D, Parsa, Afshin, Liu, Yongmei, van Duijn, Cornelia M, Siscovick, David S, Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B, Sanna, Serena, Ritchie, Marylyn D, Stricker, Bruno H, Stefansson, Kari, Boyer, Laurie A, Cappola, Thomas P, Olsen, Jesper V, Lage, Kasper, Schwartz, Peter J, Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J, Pfeufer, Arne, de Bakker, Paul I W, Newton-Cheh, Christopher, Arking, Dan E, Pulit, Sara L, Crotti, Lia, van der Harst, Pim, Munroe, Patricia B, Koopmann, Tamara T, Sotoodehnia, Nona, Rossin, Elizabeth J, Morley, Michael, Wang, Xinchen, Johnson, Andrew D, Lundby, Alicia, Gudbjartsson, Daníel F, Noseworthy, Peter A, Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V, Dörr, Marcus, Müller-Nurasyid, Martina, Lahtinen, Annukka M, Nolte, Ilja M, Smith, Albert Vernon, Bis, Joshua C, Isaacs, Aaron, Newhouse, Stephen J, Evans, Daniel S, Post, Wendy S, Waggott, Daryl, Lyytikäinen, Leo-Pekka, Hicks, Andrew A, Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J, Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W, Naluai, Asa T, Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G, Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A, Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D, Harris, Tamara B, Launer, Lenore J, Shuldiner, Alan R, Alonso, Alvaro, Bader, Joel S, Ehret, Georg, Huang, Hailiang, Kao, W H Linda, Strait, James B, Macfarlane, Peter W, Brown, Morris, Caulfield, Mark J, Samani, Nilesh J, Kronenberg, Florian, Willeit, Johann, Smith, J Gustav, Greiser, Karin H, Meyer Zu Schwabedissen, Henriette, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R, Psaty, Bruce M, Rotter, Jerome I, Kolcic, Ivana, Polašek, Ozren, Wright, Alan F, Griffin, Maura, Daly, Mark J, Arnar, David O, Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C, Roden, Dan M, Zuvich, Rebecca L, Emilsson, Valur, Plump, Andrew S, Larson, Martin G, O'Donnell, Christopher J, Yin, Xiaoyan, Bobbo, Marco, D'Adamo, Adamo P, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R, Nalls, Michael A, Jula, Antti, Kontula, Kimmo K, Marjamaa, Annukka, Oikarinen, Lasse, Perola, Markus, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl-Heinz, Kälsch, Hagen, Nöthen, Markus M, den Hoed, Marcel, Loos, Ruth J F, Thelle, Dag S, Gieger, Christian, Meitinger, Thomas, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F, Waldenberger, Melanie, de Boer, Rudolf A, Franke, Lude, van der Vleuten, Pieter A, Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A M, Behr, Elijah R, Dalageorgou, Chrysoula, Giudicessi, John R, Medeiros-Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M, Scherer, Stephen W, Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E, Greco M, Fabiola Del, Fuchsberger, Christian, O'Connell, Jeffrey R, Lee, Wai K, Watt, Graham C M, Campbell, Harry, Wild, Sarah H, El Mokhtari, Nour E, Frey, Norbert, Asselbergs, Folkert W, Mateo Leach, Irene, Navis, Gerjan, van den Berg, Maarten P, van Veldhuisen, Dirk J, Kellis, Manolis, Krijthe, Bouwe P, Franco, Oscar H, Hofman, Albert, Kors, Jan A, Uitterlinden, André G, Witteman, Jacqueline C M, Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A, Abecasis, Gonçalo R, Lakatta, Edward G, Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R P, Völker, Uwe, Snieder, Harold, Spector, Timothy D, Ärnlöv, Johan, Lind, Lars, Sundström, Johan, Syvänen, Ann-Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T, Viikari, Jorma S, Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N, Paulweber, Bernhard, Haerting, Johannes, Dominiczak, Anna F, Nyberg, Fredrik, Whincup, Peter H, Hingorani, Aroon D, Schott, Jean-Jacques, Bezzina, Connie R, Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F, Rudan, Igor, Franke, Andre, Mühleisen, Thomas W, Pramstaller, Peter P, Lehtimäki, Terho J, Paterson, Andrew D, Parsa, Afshin, Liu, Yongmei, van Duijn, Cornelia M, Siscovick, David S, Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B, Sanna, Serena, Ritchie, Marylyn D, Stricker, Bruno H, Stefansson, Kari, Boyer, Laurie A, Cappola, Thomas P, Olsen, Jesper V, Lage, Kasper, Schwartz, Peter J, Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J, Pfeufer, Arne, de Bakker, Paul I W, and Newton-Cheh, Christopher
- Abstract
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
- Published
- 2014
- Full Text
- View/download PDF
46. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
- Author
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Mahajan, Anubha, Go, Min Jin, Zhang, Weihua, Below, Jennifer E, Gaulton, Kyle J, Ferreira, Teresa, Horikoshi, Momoko, Johnson, Andrew D, Ng, Maggie C Y, Prokopenko, Inga, Saleheen, Danish, Wang, Xu, Zeggini, Eleftheria, Abecasis, Goncalo R, Adair, Linda S, Almgren, Peter, Atalay, Mustafa, Aung, Tin, Baldassarre, Damiano, Balkau, Beverley, Bao, Yuqian, Barnett, Anthony H, Barroso, Ines, Basit, Abdul, Been, Latonya F, Beilby, John, Bell, Graeme I, Benediktsson, Rafn, Bergman, Richard N, Boehm, Bernhard O, Boerwinkle, Eric, Bonnycastle, Lori L, Burtt, Noel, Cai, Qiuyin, Campbell, Harry, Carey, Jason, Cauchi, Stephane, Caulfield, Mark, Chan, Juliana C N, Chang, Li-Ching, Chang, Tien-Jyun, Chang, Yi-Cheng, Charpentier, Guillaume, Chen, Chien-Hsiun, Chen, Han, Chen, Yuan-Tsong, Chia, Kee-Seng, Chidambaram, Manickam, Chines, Peter S, Cho, Nam H, Cho, Young Min, Chuang, Lee-Ming, Collins, Francis S, Cornelis, Marilyn C, Couper, David J, Crenshaw, Andrew T, van Dam, Rob M, Danesh, John, Das, Debashish, de Faire, Ulf, Dedoussis, George, Deloukas, Panos, Dimas, Antigone S, Dina, Christian, Doney, Alex S F, Donnelly, Peter J, Dorkhan, Mozhgan, van Duijn, Cornelia, Dupuis, Josee, Edkins, Sarah, Elliott, Paul, Emilsson, Valur, Erbel, Raimund, Eriksson, Johan G, Escobedo, Jorge, Esko, Tonu, Eury, Elodie, Florez, Jose C, Fontanillas, Pierre, Forouhi, Nita G, Forsen, Tom, Fox, Caroline, Fraser, Ross M, Frayling, Timothy M, Froguel, Philippe, Frossard, Philippe, Gao, Yutang, Gertow, Karl, Gieger, Christian, Gigante, Bruna, Grallert, Harald, Grant, George B, Groop, Leif C, Groves, Christopher J, Grundberg, Elin, Guiducci, Candace, Hamsten, Anders, Han, Bok-Ghee, Hara, Kazuo, Hassanali, Neelam, Hattersley, Andrew T, Hayward, Caroline, Hedman, Asa K, Herder, Christian, Hofman, Albert, Holmen, Oddgeir L, Hovingh, Kees, Hreidarsson, Astradur B, Hu, Cheng, Hu, Frank B, Hui, Jennie, Humphries, Steve E, Hunt, Sarah E, Hunter, David J, Hveem, Kristian, Hydrie, Zafar I, Ikegami, Hiroshi, Illig, Thomas, Ingelsson, Erik, Islam, Muhammed, Isomaa, Bo, Jackson, Anne U, Jafar, Tazeen, James, Alan, Jia, Weiping, Jockel, Karl-Heinz, Jonsson, Anna, Jowett, Jeremy B M, Kadowaki, Takashi, Kang, Hyun Min, Kanoni, Stavroula, Kao, Wen Hong L, Kathiresan, Sekar, Kato, Norihiro, Katulanda, Prasad, Keinanen-Kiukaanniemi, Sirkka M, Kelly, Ann M, Khan, Hassan, Khaw, Kay-Tee, Khor, Chiea-Chuen, Kim, Hyung-Lae, Kim, Sangsoo, Kim, Young Jin, Kinnunen, Leena, Klopp, Norman, Kong, Augustine, Korpi-Hyovalti, Eeva, Kowlessur, Sudhir, Kraft, Peter, Kravic, Jasmina, Kristensen, Malene M, Krithika, S, Kumar, Ashish, Kumate, Jesus, Kuusisto, Johanna, Kwak, Soo Heon, Laakso, Markku, Lagou, Vasiliki, Lakka, Timo A, Langenberg, Claudia, Langford, Cordelia, Lawrence, Robert, Leander, Karin, Lee, Jen-Mai, Lee, Nanette R, Li, Man, Li, Xinzhong, Li, Yun, Liang, Junbin, Liju, Samuel, Lim, Wei-Yen, Lind, Lars, Lindgren, Cecilia M, Lindholm, Eero, Liu, Ching-Ti, Liu, Jian Jun, Lobbens, Stephane, Long, Jirong, Loos, Ruth J F, Lu, Wei, Luan, Jian'an, Lyssenko, Valeriya, Ma, Ronald C W, Maeda, Shiro, Magi, Reedik, Mannisto, Satu, Matthews, David R, Meigs, James B, Melander, Olle, Metspalu, Andres, Meyer, Julia, Mirza, Ghazala, Mihailov, Evelin, Moebus, Susanne, Mohan, Viswanathan, Mohlke, Karen L, Morris, Andrew D, Muhleisen, Thomas W, Muller-Nurasyid, Martina, Musk, Bill, Nakamura, Jiro, Nakashima, Eitaro, Navarro, Pau, Ng, Peng-Keat, Nica, Alexandra C, Nilsson, Peter M, Njolstad, Inger, Nothen, Markus M, Ohnaka, Keizo, Ong, Twee Hee, Owen, Katharine R, Palmer, Colin N A, Pankow, James S, Park, Kyong Soo, Parkin, Melissa, Pechlivanis, Sonali, Pedersen, Nancy L, Peltonen, Leena, Perry, John R B, Peters, Annette, Pinidiyapathirage, Janani M, Platou, Carl G P, Potter, Simon, Price, Jackie F, Qi, Lu, Radha, Venkatesan, Rallidis, Loukianos, Rasheed, Asif, Rathmann, Wolfgang, Rauramaa, Rainer, Raychaudhuri, Soumya, Rayner, N William, Rees, Simon D, Rehnberg, Emil, Ripatti, Samuli, Robertson, Neil, Roden, Michael, Rossin, Elizabeth J, Rudan, Igor, Rybin, Denis, Saaristo, Timo E, Salomaa, Veikko, Saltevo, Juha, Samuel, Maria, Sanghera, Dharambir K, Saramies, Jouko, Scott, James, Scott, Laura J, Scott, Robert A, Segre, Ayellet V, Sehmi, Joban, Sennblad, Bengt, Shah, Nabi, Shah, Sonia, Shera, A Samad, Shu, Xiao Ou, Shuldiner, Alan R, Sigurðsson, Gunnar, Sijbrands, Eric, Silveira, Angela, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S, So, Wing Yee, Stancakova, Alena, Stefansson, Kari, Steinbach, Gerald, Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Strawbridge, Rona J, Stringham, Heather M, Sun, Qi, Suo, Chen, Syvänen, Ann-Christine, Takayanagi, Ryoichi, Takeuchi, Fumihiko, Tay, Wan Ting, Teslovich, Tanya M, Thorand, Barbara, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tikkanen, Emmi, Trakalo, Joseph, Tremoli, Elena, Trip, Mieke D, Tsai, Fuu Jen, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Uitterlinden, Andre G, Valladares-Salgado, Adan, Vedantam, Sailaja, Veglia, Fabrizio, Voight, Benjamin F, Wang, Congrong, Wareham, Nicholas J, Wennauer, Roman, Wickremasinghe, Ananda R, Wilsgaard, Tom, Wilson, James F, Wiltshire, Steven, Winckler, Wendy, Wong, Tien Yin, Wood, Andrew R, Wu, Jer-Yuarn, Wu, Ying, Yamamoto, Ken, Yamauchi, Toshimasa, Yang, Mingyu, Yengo, Loic, Yokota, Mitsuhiro, Young, Robin, Zabaneh, Delilah, Zhang, Fan, Zhang, Rong, Zheng, Wei, Zimmet, Paul Z, Altshuler, David, Bowden, Donald W, Cho, Yoon Shin, Cox, Nancy J, Cruz, Miguel, Hanis, Craig L, Kooner, Jaspal, Lee, Jong-Young, Seielstad, Mark, Teo, Yik Ying, Boehnke, Michael, Parra, Esteban J, Chambers, John C, Tai, E Shyong, McCarthy, Mark I, Morris, Andrew P, Mahajan, Anubha, Go, Min Jin, Zhang, Weihua, Below, Jennifer E, Gaulton, Kyle J, Ferreira, Teresa, Horikoshi, Momoko, Johnson, Andrew D, Ng, Maggie C Y, Prokopenko, Inga, Saleheen, Danish, Wang, Xu, Zeggini, Eleftheria, Abecasis, Goncalo R, Adair, Linda S, Almgren, Peter, Atalay, Mustafa, Aung, Tin, Baldassarre, Damiano, Balkau, Beverley, Bao, Yuqian, Barnett, Anthony H, Barroso, Ines, Basit, Abdul, Been, Latonya F, Beilby, John, Bell, Graeme I, Benediktsson, Rafn, Bergman, Richard N, Boehm, Bernhard O, Boerwinkle, Eric, Bonnycastle, Lori L, Burtt, Noel, Cai, Qiuyin, Campbell, Harry, Carey, Jason, Cauchi, Stephane, Caulfield, Mark, Chan, Juliana C N, Chang, Li-Ching, Chang, Tien-Jyun, Chang, Yi-Cheng, Charpentier, Guillaume, Chen, Chien-Hsiun, Chen, Han, Chen, Yuan-Tsong, Chia, Kee-Seng, Chidambaram, Manickam, Chines, Peter S, Cho, Nam H, Cho, Young Min, Chuang, Lee-Ming, Collins, Francis S, Cornelis, Marilyn C, Couper, David J, Crenshaw, Andrew T, van Dam, Rob M, Danesh, John, Das, Debashish, de Faire, Ulf, Dedoussis, George, Deloukas, Panos, Dimas, Antigone S, Dina, Christian, Doney, Alex S F, Donnelly, Peter J, Dorkhan, Mozhgan, van Duijn, Cornelia, Dupuis, Josee, Edkins, Sarah, Elliott, Paul, Emilsson, Valur, Erbel, Raimund, Eriksson, Johan G, Escobedo, Jorge, Esko, Tonu, Eury, Elodie, Florez, Jose C, Fontanillas, Pierre, Forouhi, Nita G, Forsen, Tom, Fox, Caroline, Fraser, Ross M, Frayling, Timothy M, Froguel, Philippe, Frossard, Philippe, Gao, Yutang, Gertow, Karl, Gieger, Christian, Gigante, Bruna, Grallert, Harald, Grant, George B, Groop, Leif C, Groves, Christopher J, Grundberg, Elin, Guiducci, Candace, Hamsten, Anders, Han, Bok-Ghee, Hara, Kazuo, Hassanali, Neelam, Hattersley, Andrew T, Hayward, Caroline, Hedman, Asa K, Herder, Christian, Hofman, Albert, Holmen, Oddgeir L, Hovingh, Kees, Hreidarsson, Astradur B, Hu, Cheng, Hu, Frank B, Hui, Jennie, Humphries, Steve E, Hunt, Sarah E, Hunter, David J, Hveem, Kristian, Hydrie, Zafar I, Ikegami, Hiroshi, Illig, Thomas, Ingelsson, Erik, Islam, Muhammed, Isomaa, Bo, Jackson, Anne U, Jafar, Tazeen, James, Alan, Jia, Weiping, Jockel, Karl-Heinz, Jonsson, Anna, Jowett, Jeremy B M, Kadowaki, Takashi, Kang, Hyun Min, Kanoni, Stavroula, Kao, Wen Hong L, Kathiresan, Sekar, Kato, Norihiro, Katulanda, Prasad, Keinanen-Kiukaanniemi, Sirkka M, Kelly, Ann M, Khan, Hassan, Khaw, Kay-Tee, Khor, Chiea-Chuen, Kim, Hyung-Lae, Kim, Sangsoo, Kim, Young Jin, Kinnunen, Leena, Klopp, Norman, Kong, Augustine, Korpi-Hyovalti, Eeva, Kowlessur, Sudhir, Kraft, Peter, Kravic, Jasmina, Kristensen, Malene M, Krithika, S, Kumar, Ashish, Kumate, Jesus, Kuusisto, Johanna, Kwak, Soo Heon, Laakso, Markku, Lagou, Vasiliki, Lakka, Timo A, Langenberg, Claudia, Langford, Cordelia, Lawrence, Robert, Leander, Karin, Lee, Jen-Mai, Lee, Nanette R, Li, Man, Li, Xinzhong, Li, Yun, Liang, Junbin, Liju, Samuel, Lim, Wei-Yen, Lind, Lars, Lindgren, Cecilia M, Lindholm, Eero, Liu, Ching-Ti, Liu, Jian Jun, Lobbens, Stephane, Long, Jirong, Loos, Ruth J F, Lu, Wei, Luan, Jian'an, Lyssenko, Valeriya, Ma, Ronald C W, Maeda, Shiro, Magi, Reedik, Mannisto, Satu, Matthews, David R, Meigs, James B, Melander, Olle, Metspalu, Andres, Meyer, Julia, Mirza, Ghazala, Mihailov, Evelin, Moebus, Susanne, Mohan, Viswanathan, Mohlke, Karen L, Morris, Andrew D, Muhleisen, Thomas W, Muller-Nurasyid, Martina, Musk, Bill, Nakamura, Jiro, Nakashima, Eitaro, Navarro, Pau, Ng, Peng-Keat, Nica, Alexandra C, Nilsson, Peter M, Njolstad, Inger, Nothen, Markus M, Ohnaka, Keizo, Ong, Twee Hee, Owen, Katharine R, Palmer, Colin N A, Pankow, James S, Park, Kyong Soo, Parkin, Melissa, Pechlivanis, Sonali, Pedersen, Nancy L, Peltonen, Leena, Perry, John R B, Peters, Annette, Pinidiyapathirage, Janani M, Platou, Carl G P, Potter, Simon, Price, Jackie F, Qi, Lu, Radha, Venkatesan, Rallidis, Loukianos, Rasheed, Asif, Rathmann, Wolfgang, Rauramaa, Rainer, Raychaudhuri, Soumya, Rayner, N William, Rees, Simon D, Rehnberg, Emil, Ripatti, Samuli, Robertson, Neil, Roden, Michael, Rossin, Elizabeth J, Rudan, Igor, Rybin, Denis, Saaristo, Timo E, Salomaa, Veikko, Saltevo, Juha, Samuel, Maria, Sanghera, Dharambir K, Saramies, Jouko, Scott, James, Scott, Laura J, Scott, Robert A, Segre, Ayellet V, Sehmi, Joban, Sennblad, Bengt, Shah, Nabi, Shah, Sonia, Shera, A Samad, Shu, Xiao Ou, Shuldiner, Alan R, Sigurðsson, Gunnar, Sijbrands, Eric, Silveira, Angela, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S, So, Wing Yee, Stancakova, Alena, Stefansson, Kari, Steinbach, Gerald, Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Strawbridge, Rona J, Stringham, Heather M, Sun, Qi, Suo, Chen, Syvänen, Ann-Christine, Takayanagi, Ryoichi, Takeuchi, Fumihiko, Tay, Wan Ting, Teslovich, Tanya M, Thorand, Barbara, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tikkanen, Emmi, Trakalo, Joseph, Tremoli, Elena, Trip, Mieke D, Tsai, Fuu Jen, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Uitterlinden, Andre G, Valladares-Salgado, Adan, Vedantam, Sailaja, Veglia, Fabrizio, Voight, Benjamin F, Wang, Congrong, Wareham, Nicholas J, Wennauer, Roman, Wickremasinghe, Ananda R, Wilsgaard, Tom, Wilson, James F, Wiltshire, Steven, Winckler, Wendy, Wong, Tien Yin, Wood, Andrew R, Wu, Jer-Yuarn, Wu, Ying, Yamamoto, Ken, Yamauchi, Toshimasa, Yang, Mingyu, Yengo, Loic, Yokota, Mitsuhiro, Young, Robin, Zabaneh, Delilah, Zhang, Fan, Zhang, Rong, Zheng, Wei, Zimmet, Paul Z, Altshuler, David, Bowden, Donald W, Cho, Yoon Shin, Cox, Nancy J, Cruz, Miguel, Hanis, Craig L, Kooner, Jaspal, Lee, Jong-Young, Seielstad, Mark, Teo, Yik Ying, Boehnke, Michael, Parra, Esteban J, Chambers, John C, Tai, E Shyong, McCarthy, Mark I, and Morris, Andrew P
- Abstract
To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry., Consortium, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM)Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D)Consortium, South Asian Type 2 Diabetes (SAT2D)Consortium, Mexican American Type 2 Diabetes (MAT2D)Consortium, Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES)
- Published
- 2014
- Full Text
- View/download PDF
47. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics
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Lundby, Alicia, Rossin, Elizabeth J, Steffensen, Annette B, Acha, Moshe Rav, Newton-Cheh, Christopher, Pfeufer, Arne, Lynch, Stacey N, Olesen, Søren-Peter, Brunak, Søren, Ellinor, Patrick T, Jukema, J Wouter, Trompet, Stella, Ford, Ian, Macfarlane, Peter W, Krijthe, Bouwe P, Hofman, Albert, Uitterlinden, André G, Stricker, Bruno H, Nathoe, Hendrik M, Spiering, Wilko, Daly, Mark J, Asselbergs, Folkert W, van der Harst, Pim, Milan, David J, de Bakker, Paul I W, Hansen, Kasper Lage, Olsen, Jesper V, Lundby, Alicia, Rossin, Elizabeth J, Steffensen, Annette B, Acha, Moshe Rav, Newton-Cheh, Christopher, Pfeufer, Arne, Lynch, Stacey N, Olesen, Søren-Peter, Brunak, Søren, Ellinor, Patrick T, Jukema, J Wouter, Trompet, Stella, Ford, Ian, Macfarlane, Peter W, Krijthe, Bouwe P, Hofman, Albert, Uitterlinden, André G, Stricker, Bruno H, Nathoe, Hendrik M, Spiering, Wilko, Daly, Mark J, Asselbergs, Folkert W, van der Harst, Pim, Milan, David J, de Bakker, Paul I W, Hansen, Kasper Lage, and Olsen, Jesper V
- Abstract
Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes involved in the Mendelian disorder long QT syndrome (LQTS). We integrated the LQTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LQTS protein network to filter weak GWAS signals by identifying single-nucleotide polymorphisms (SNPs) in proximity to genes in the network supported by strong proteomic evidence. Three SNPs passing this filter reached genome-wide significance after replication genotyping. Overall, we present a general strategy to propose candidates in GWAS loci for functional studies and to systematically filter subtle association signals using tissue-specific quantitative interaction proteomics.
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- 2014
48. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
- Author
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den Hoed, Marcel, Eijgelsheim, Mark, Esko, Tonu, Brundel, Bianca J. J. M., Peal, David S., Evans, David M., Nolte, Ilja M., Segre, Ayellet V., Holm, Hilma, Handsaker, Robert E., Westra, Harm-Jan, Johnson, Toby, Isaacs, Aaron, Yang, Jian, Lundby, Alicia, Zhao, Jing Hua, Kim, Young Jin, Go, Min Jin, Almgren, Peter, Bochud, Murielle, Boucher, Gabrielle, Cornelis, Marilyn C., Gudbjartsson, Daniel, Hadley, David, van der Harst, Pim, Hayward, Caroline, den Heijer, Martin, Igl, Wilmar, Jackson, Anne U., Kutalik, Zoltan, Luan, Jian'an, Kemp, John P., Kristiansson, Kati, Ladenvall, Claes, Lorentzon, Mattias, Montasser, May E., Njajou, Omer T., O'Reilly, Paul F., Padmanabhan, Sandosh, Pourcain, Beate St., Rankinen, Tuomo, Salo, Perttu, Tanaka, Toshiko, Timpson, Nicholas J., Vitart, Veronique, Waite, Lindsay, Wheeler, William, Zhang, Weihua, Draisma, Harmen H. M., Feitosa, Mary F., Kerr, Kathleen F., Lind, Penelope A., Mihailov, Evelin, Onland-Moret, N. Charlotte, Song, Ci, Weedon, Michael N., Xie, Weijia, Yengo, Loic, Absher, Devin, Albert, Christine M., Alonso, Alvaro, Arking, Dan E., de Bakker, Paul I. W., Balkau, Beverley, Barlassina, Cristina, Benaglio, Paola, Bis, Joshua C., Bouatia-Naji, Nabila, Brage, Soren, Chanock, Stephen J., Chines, Peter S., Chung, Mina, Darbar, Dawood, Dina, Christian, Doerr, Marcus, Elliott, Paul, Felix, Stephan B., Fischer, Krista, Fuchsberger, Christian, de Geus, Eco J. C., Goyette, Philippe, Gudnason, Vilmundur, Harris, Tamara B., Hartikainen, Anna-Liisa, Havulinna, Aki S., Heckbert, Susan R., Hicks, Andrew A., Hofman, Albert, Holewijn, Suzanne, Hoogstra-Berends, Femke, Hottenga, Jouke-Jan, Jensen, Majken K., Johansson, Asa, Junttila, Juhani, Kaeaeb, Stefan, Kanon, Bart, Ketkar, Shamika, Khaw, Kay-Tee, Knowles, Joshua W., Kooner, Angrad S., Kors, Jan A., Kumari, Meena, Milani, Lili, Laiho, Paeivi, Lakatta, Edward G., Langenberg, Claudia, Leusink, Maarten, Liu, Yongmei, Luben, Robert N., Lunetta, Kathryn L., Lynch, Stacey N., Markus, Marcello R. P., Marques-Vidal, Pedro, Leach, Irene Mateo, McArdle, Wendy L., McCarroll, Steven A., Medland, Sarah E., Miller, Kathryn A., Montgomery, Grant W., Morrison, Alanna C., Mueller-Nurasyid, Martina, Navarro, Pau, Nelis, Mari, O'Connell, Jeffrey R., O'Donnell, Christopher J., Ong, Ken K., Newman, Anne B., Peters, Annette, Polasek, Ozren, Pouta, Anneli, Pramstaller, Peter P., Psaty, Bruce M., Rao, Dabeeru C., Ring, Susan M., Rossin, Elizabeth J., Rudan, Diana, Sanna, Serena, Scott, Robert A., Sehmi, Jaban S., Sharp, Stephen, Shin, Jordan T., Singleton, Andrew B., Smith, Albert V., Soranzo, Nicole, Spector, Tim D., Stewart, Chip, Stringham, Heather M., Tarasov, Kirill V., Uitterlinden, Andre G., Vandenput, Liesbeth, Hwang, Shih-Jen, Whitfield, John B., Wijmenga, Cisca, Wild, Sarah H., Willemsen, Gonneke, Wilson, James F., Witteman, Jacqueline C. M., Wong, Andrew, Wong, Quenna, Jamshidi, Yalda, Zitting, Paavo, Boer, Jolanda M. A., Boomsma, Dorret I., Borecki, Ingrid B., van Duijn, Cornelia M., Ekelund, Ulf, Forouhi, Nita G., Froguel, Philippe, Hingorani, Aroon, Ingelsson, Erik, Kivimaki, Mika, Kronmal, Richard A., Kuh, Diana, Lind, Lars, Martin, Nicholas G., Oostra, Ben A., Pedersen, Nancy L., Quertermous, Thomas, Rotter, Jerome I., van der Schouw, Yvonne T., Verschuren, W. M. Monique, Walker, Mark, Albanes, Demetrius, Arnar, David O., Assimes, Themistocles L., Bandinelli, Stefania, Boehnke, Michael, de Boer, Rudolf A., Bouchard, Claude, Caulfield, W. L. Mark, Chambers, John C., Curhan, Gary, Cusi, Daniele, Eriksson, Johan, Ferrucci, Luigi, van Gilst, Wiek H., Glorioso, Nicola, de Graaf, Jacqueline, Groop, Leif, Gyllensten, Ulf, Hsueh, Wen-Chi, Hu, Frank B., Huikuri, Heikki V., Hunter, David J., Iribarren, Carlos, Isomaa, Bo, Jarvelin, Marjo-Riitta, Jula, Antti, Kahonen, Mika, Kiemeney, Lambertus A., van der Klauw, Melanie M., Kooner, Jaspal S., Kraft, Peter, Iacoviello, Licia, Lehtimaki, Terho, Lokki, Marja-Liisa L., Mitchell, Braxton D., Navis, Gerjan, Nieminen, Markku S., Ohlsson, Claes, Poulter, Neil R., Qi, Lu, Raitakari, Olli T., Rimm, Eric B., Rioux, John D., Rizzi, Federica, Rudan, Igor, Salomaa, Veikko, Sever, Peter S., Shields, Denis C., Shuldiner, Alan R., Sinisalo, Juha, Stanton, Alice V., Stolk, Ronald P., Strachan, David P., Tardif, Jean-Claude, Thorsteinsdottir, Unnur, Tuomilehto, Jaako, van Veldhuisen, Dirk J., Virtamo, Jarmo, Viikari, Jorma, Vollenweider, Peter, Waeber, Gerard, Widen, Elisabeth, Cho, Yoon Shin, Olsen, Jesper V., Visscher, Peter M., Willer, Cristen, Franke, Lude, Erdmann, Jeanette, Thompson, John R., Pfeufer, Arne, Sotoodehnia, Nona, Newton-Cheh, Christopher, Ellinor, Patrick T., Stricker, Bruno H. Ch, Metspalu, Andres, Perola, Markus, Beckmann, Jacques S., Smith, George Davey, Stefansson, Kari, Wareham, Nicholas J., Munroe, Patricia B., Sibon, Ody C. M., Milan, David J., Snieder, Harold, Samani, Nilesh J., Loos, Ruth J. F., den Hoed, Marcel, Eijgelsheim, Mark, Esko, Tonu, Brundel, Bianca J. J. M., Peal, David S., Evans, David M., Nolte, Ilja M., Segre, Ayellet V., Holm, Hilma, Handsaker, Robert E., Westra, Harm-Jan, Johnson, Toby, Isaacs, Aaron, Yang, Jian, Lundby, Alicia, Zhao, Jing Hua, Kim, Young Jin, Go, Min Jin, Almgren, Peter, Bochud, Murielle, Boucher, Gabrielle, Cornelis, Marilyn C., Gudbjartsson, Daniel, Hadley, David, van der Harst, Pim, Hayward, Caroline, den Heijer, Martin, Igl, Wilmar, Jackson, Anne U., Kutalik, Zoltan, Luan, Jian'an, Kemp, John P., Kristiansson, Kati, Ladenvall, Claes, Lorentzon, Mattias, Montasser, May E., Njajou, Omer T., O'Reilly, Paul F., Padmanabhan, Sandosh, Pourcain, Beate St., Rankinen, Tuomo, Salo, Perttu, Tanaka, Toshiko, Timpson, Nicholas J., Vitart, Veronique, Waite, Lindsay, Wheeler, William, Zhang, Weihua, Draisma, Harmen H. M., Feitosa, Mary F., Kerr, Kathleen F., Lind, Penelope A., Mihailov, Evelin, Onland-Moret, N. Charlotte, Song, Ci, Weedon, Michael N., Xie, Weijia, Yengo, Loic, Absher, Devin, Albert, Christine M., Alonso, Alvaro, Arking, Dan E., de Bakker, Paul I. W., Balkau, Beverley, Barlassina, Cristina, Benaglio, Paola, Bis, Joshua C., Bouatia-Naji, Nabila, Brage, Soren, Chanock, Stephen J., Chines, Peter S., Chung, Mina, Darbar, Dawood, Dina, Christian, Doerr, Marcus, Elliott, Paul, Felix, Stephan B., Fischer, Krista, Fuchsberger, Christian, de Geus, Eco J. C., Goyette, Philippe, Gudnason, Vilmundur, Harris, Tamara B., Hartikainen, Anna-Liisa, Havulinna, Aki S., Heckbert, Susan R., Hicks, Andrew A., Hofman, Albert, Holewijn, Suzanne, Hoogstra-Berends, Femke, Hottenga, Jouke-Jan, Jensen, Majken K., Johansson, Asa, Junttila, Juhani, Kaeaeb, Stefan, Kanon, Bart, Ketkar, Shamika, Khaw, Kay-Tee, Knowles, Joshua W., Kooner, Angrad S., Kors, Jan A., Kumari, Meena, Milani, Lili, Laiho, Paeivi, Lakatta, Edward G., Langenberg, Claudia, Leusink, Maarten, Liu, Yongmei, Luben, Robert N., Lunetta, Kathryn L., Lynch, Stacey N., Markus, Marcello R. P., Marques-Vidal, Pedro, Leach, Irene Mateo, McArdle, Wendy L., McCarroll, Steven A., Medland, Sarah E., Miller, Kathryn A., Montgomery, Grant W., Morrison, Alanna C., Mueller-Nurasyid, Martina, Navarro, Pau, Nelis, Mari, O'Connell, Jeffrey R., O'Donnell, Christopher J., Ong, Ken K., Newman, Anne B., Peters, Annette, Polasek, Ozren, Pouta, Anneli, Pramstaller, Peter P., Psaty, Bruce M., Rao, Dabeeru C., Ring, Susan M., Rossin, Elizabeth J., Rudan, Diana, Sanna, Serena, Scott, Robert A., Sehmi, Jaban S., Sharp, Stephen, Shin, Jordan T., Singleton, Andrew B., Smith, Albert V., Soranzo, Nicole, Spector, Tim D., Stewart, Chip, Stringham, Heather M., Tarasov, Kirill V., Uitterlinden, Andre G., Vandenput, Liesbeth, Hwang, Shih-Jen, Whitfield, John B., Wijmenga, Cisca, Wild, Sarah H., Willemsen, Gonneke, Wilson, James F., Witteman, Jacqueline C. M., Wong, Andrew, Wong, Quenna, Jamshidi, Yalda, Zitting, Paavo, Boer, Jolanda M. A., Boomsma, Dorret I., Borecki, Ingrid B., van Duijn, Cornelia M., Ekelund, Ulf, Forouhi, Nita G., Froguel, Philippe, Hingorani, Aroon, Ingelsson, Erik, Kivimaki, Mika, Kronmal, Richard A., Kuh, Diana, Lind, Lars, Martin, Nicholas G., Oostra, Ben A., Pedersen, Nancy L., Quertermous, Thomas, Rotter, Jerome I., van der Schouw, Yvonne T., Verschuren, W. M. Monique, Walker, Mark, Albanes, Demetrius, Arnar, David O., Assimes, Themistocles L., Bandinelli, Stefania, Boehnke, Michael, de Boer, Rudolf A., Bouchard, Claude, Caulfield, W. L. Mark, Chambers, John C., Curhan, Gary, Cusi, Daniele, Eriksson, Johan, Ferrucci, Luigi, van Gilst, Wiek H., Glorioso, Nicola, de Graaf, Jacqueline, Groop, Leif, Gyllensten, Ulf, Hsueh, Wen-Chi, Hu, Frank B., Huikuri, Heikki V., Hunter, David J., Iribarren, Carlos, Isomaa, Bo, Jarvelin, Marjo-Riitta, Jula, Antti, Kahonen, Mika, Kiemeney, Lambertus A., van der Klauw, Melanie M., Kooner, Jaspal S., Kraft, Peter, Iacoviello, Licia, Lehtimaki, Terho, Lokki, Marja-Liisa L., Mitchell, Braxton D., Navis, Gerjan, Nieminen, Markku S., Ohlsson, Claes, Poulter, Neil R., Qi, Lu, Raitakari, Olli T., Rimm, Eric B., Rioux, John D., Rizzi, Federica, Rudan, Igor, Salomaa, Veikko, Sever, Peter S., Shields, Denis C., Shuldiner, Alan R., Sinisalo, Juha, Stanton, Alice V., Stolk, Ronald P., Strachan, David P., Tardif, Jean-Claude, Thorsteinsdottir, Unnur, Tuomilehto, Jaako, van Veldhuisen, Dirk J., Virtamo, Jarmo, Viikari, Jorma, Vollenweider, Peter, Waeber, Gerard, Widen, Elisabeth, Cho, Yoon Shin, Olsen, Jesper V., Visscher, Peter M., Willer, Cristen, Franke, Lude, Erdmann, Jeanette, Thompson, John R., Pfeufer, Arne, Sotoodehnia, Nona, Newton-Cheh, Christopher, Ellinor, Patrick T., Stricker, Bruno H. Ch, Metspalu, Andres, Perola, Markus, Beckmann, Jacques S., Smith, George Davey, Stefansson, Kari, Wareham, Nicholas J., Munroe, Patricia B., Sibon, Ody C. M., Milan, David J., Snieder, Harold, Samani, Nilesh J., and Loos, Ruth J. F.
- Abstract
Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
- Published
- 2013
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49. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes
- Author
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Morris, Andrew P., Voight, Benjamin F., Teslovich, Tanya M., Ferreira, Teresa, Segre, Ayellet V., Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Khan, Hassan, Grallert, Harald, Mahajan, Anubha, Prokopenko, Inga, Kang, Hyun Min, Dina, Christian, Esko, Tonu, Fraser, Ross M., Kanoni, Stavroula, Kumar, Ashish, Lagou, Vasiliki, Langenberg, Claudia, Luan, Jian'an, Lindgren, Cecilia M., Mueller-Nurasyid, Martina, Pechlivanis, Sonali, Rayner, N. William, Scott, Laura J., Wiltshire, Steven, Yengo, Loic, Kinnunen, Leena, Rossin, Elizabeth J., Raychaudhuri, Soumya, Johnson, Andrew D., Dimas, Antigone S., Loos, Ruth J. F., Vedantam, Sailaja, Chen, Han, Florez, Jose C., Fox, Caroline, Liu, Ching-Ti, Rybin, Denis, Couper, David J., Kao, Wen Hong L., Li, Man, Cornelis, Marilyn C., Kraft, Peter, Sun, Qi, van Dam, Rob M., Stringham, Heather M., Chines, Peter S., Fischer, Krista, Fontanillas, Pierre, Holmen, Oddgeir L., Hunt, Sarah E., Jackson, Anne U., Kong, Augustine, Lawrence, Robert, Meyer, Julia, Perry, John R. B., Platou, Carl G. P., Potter, Simon, Rehnberg, Emil, Robertson, Neil, Sivapalaratnam, Suthesh, Stancakova, Alena, Stirrups, Kathleen, Thorleifsson, Gudmar, Tikkanen, Emmi, Wood, Andrew R., Almgren, Peter, Atalay, Mustafa, Benediktsson, Rafn, Bonnycastle, Lori L., Burtt, Noel, Carey, Jason, Charpentier, Guillaume, Crenshaw, Andrew T., Doney, Alex S. F., Dorkhan, Mozhgan, Edkins, Sarah, Emilsson, Valur, Eury, Elodie, Forsen, Tom, Gertow, Karl, Gigante, Bruna, Grant, George B., Groves, Christopher J., Guiducci, Candace, Herder, Christian, Hreidarsson, Astradur B., Hui, Jennie, James, Alan, Jonsson, Anna, Rathmann, Wolfgang, Klopp, Norman, Kravic, Jasmina, Krjutskov, Kaarel, Langford, Cordelia, Leander, Karin, Lindholm, Eero, Lobbens, Stephane, Mannisto, Satu, Mirza, Ghazala, Muehleisen, Thomas W., Musk, Bill, Parkin, Melissa, Rallidis, Loukianos, Saramies, Jouko, Sennblad, Bengt, Shah, Sonia, Sigurdsson, Gunnar, Silveira, Angela, Steinbach, Gerald, Thorand, Barbara, Trakalo, Joseph, Veglia, Fabrizio, Wennauer, Roman, Winckler, Wendy, Zabaneh, Delilah, Campbell, Harry, van Duijn, Cornelia, Uitterlinden, Andre G., Hofman, Albert, Sijbrands, Eric, Abecasis, Goncalo R., Owen, Katharine R., Zeggini, Eleftheria, Trip, Mieke D., Forouhi, Nita G., Syvänen, Ann-Christine, Eriksson, Johan G., Peltonen, Leena, Noethen, Markus M., Balkau, Beverley, Palmer, Colin N. A., Lyssenko, Valeriya, Tuomi, Tiinamaija, Isomaa, Bo, Hunter, David J., Qi, Lu, Shuldiner, Alan R., Roden, Michael, Barroso, Ines, Wilsgaard, Tom, Beilby, John, Hovingh, Kees, Price, Jackie F., Wilson, James F., Rauramaa, Rainer, Lakka, Timo A., Lind, Lars, Dedoussis, George, Njolstad, Inger, Pedersen, Nancy L., Khaw, Kay-Tee, Wareham, Nicholas J., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Korpi-Hyovalti, Eeva, Saltevo, Juha, Laakso, Markku, Kuusisto, Johanna, Metspalu, Andres, Collins, Francis S., Mohlke, Karen L., Bergman, Richard N., Tuomilehto, Jaakko, Boehm, Bernhard O., Gieger, Christian, Hveem, Kristian, Cauchi, Stephane, Froguel, Philippe, Baldassarre, Damiano, Tremoli, Elena, Humphries, Steve E., Saleheen, Danish, Danesh, John, Ingelsson, Erik, Ripatti, Samuli, Salomaa, Veikko, Erbel, Raimund, Joeckel, Karl-Heinz, Moebus, Susanne, Peters, Annette, Illig, Thomas, de Faire, Ulf, Hamsten, Anders, Morris, Andrew D., Donnelly, Peter J., Frayling, Timothy M., Hattersley, Andrew T., Boerwinkle, Eric, Melander, Olle, Kathiresan, Sekar, Nilsson, Peter M., Deloukas, Panos, Thorsteinsdottir, Unnur, Groop, Leif C., Stefansson, Kari, Hu, Frank, Pankow, James S., Dupuis, Josee, Meigs, James B., Altshuler, David, Boehnke, Michael, McCarthy, Mark I., Morris, Andrew P., Voight, Benjamin F., Teslovich, Tanya M., Ferreira, Teresa, Segre, Ayellet V., Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Khan, Hassan, Grallert, Harald, Mahajan, Anubha, Prokopenko, Inga, Kang, Hyun Min, Dina, Christian, Esko, Tonu, Fraser, Ross M., Kanoni, Stavroula, Kumar, Ashish, Lagou, Vasiliki, Langenberg, Claudia, Luan, Jian'an, Lindgren, Cecilia M., Mueller-Nurasyid, Martina, Pechlivanis, Sonali, Rayner, N. William, Scott, Laura J., Wiltshire, Steven, Yengo, Loic, Kinnunen, Leena, Rossin, Elizabeth J., Raychaudhuri, Soumya, Johnson, Andrew D., Dimas, Antigone S., Loos, Ruth J. F., Vedantam, Sailaja, Chen, Han, Florez, Jose C., Fox, Caroline, Liu, Ching-Ti, Rybin, Denis, Couper, David J., Kao, Wen Hong L., Li, Man, Cornelis, Marilyn C., Kraft, Peter, Sun, Qi, van Dam, Rob M., Stringham, Heather M., Chines, Peter S., Fischer, Krista, Fontanillas, Pierre, Holmen, Oddgeir L., Hunt, Sarah E., Jackson, Anne U., Kong, Augustine, Lawrence, Robert, Meyer, Julia, Perry, John R. B., Platou, Carl G. P., Potter, Simon, Rehnberg, Emil, Robertson, Neil, Sivapalaratnam, Suthesh, Stancakova, Alena, Stirrups, Kathleen, Thorleifsson, Gudmar, Tikkanen, Emmi, Wood, Andrew R., Almgren, Peter, Atalay, Mustafa, Benediktsson, Rafn, Bonnycastle, Lori L., Burtt, Noel, Carey, Jason, Charpentier, Guillaume, Crenshaw, Andrew T., Doney, Alex S. F., Dorkhan, Mozhgan, Edkins, Sarah, Emilsson, Valur, Eury, Elodie, Forsen, Tom, Gertow, Karl, Gigante, Bruna, Grant, George B., Groves, Christopher J., Guiducci, Candace, Herder, Christian, Hreidarsson, Astradur B., Hui, Jennie, James, Alan, Jonsson, Anna, Rathmann, Wolfgang, Klopp, Norman, Kravic, Jasmina, Krjutskov, Kaarel, Langford, Cordelia, Leander, Karin, Lindholm, Eero, Lobbens, Stephane, Mannisto, Satu, Mirza, Ghazala, Muehleisen, Thomas W., Musk, Bill, Parkin, Melissa, Rallidis, Loukianos, Saramies, Jouko, Sennblad, Bengt, Shah, Sonia, Sigurdsson, Gunnar, Silveira, Angela, Steinbach, Gerald, Thorand, Barbara, Trakalo, Joseph, Veglia, Fabrizio, Wennauer, Roman, Winckler, Wendy, Zabaneh, Delilah, Campbell, Harry, van Duijn, Cornelia, Uitterlinden, Andre G., Hofman, Albert, Sijbrands, Eric, Abecasis, Goncalo R., Owen, Katharine R., Zeggini, Eleftheria, Trip, Mieke D., Forouhi, Nita G., Syvänen, Ann-Christine, Eriksson, Johan G., Peltonen, Leena, Noethen, Markus M., Balkau, Beverley, Palmer, Colin N. A., Lyssenko, Valeriya, Tuomi, Tiinamaija, Isomaa, Bo, Hunter, David J., Qi, Lu, Shuldiner, Alan R., Roden, Michael, Barroso, Ines, Wilsgaard, Tom, Beilby, John, Hovingh, Kees, Price, Jackie F., Wilson, James F., Rauramaa, Rainer, Lakka, Timo A., Lind, Lars, Dedoussis, George, Njolstad, Inger, Pedersen, Nancy L., Khaw, Kay-Tee, Wareham, Nicholas J., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Korpi-Hyovalti, Eeva, Saltevo, Juha, Laakso, Markku, Kuusisto, Johanna, Metspalu, Andres, Collins, Francis S., Mohlke, Karen L., Bergman, Richard N., Tuomilehto, Jaakko, Boehm, Bernhard O., Gieger, Christian, Hveem, Kristian, Cauchi, Stephane, Froguel, Philippe, Baldassarre, Damiano, Tremoli, Elena, Humphries, Steve E., Saleheen, Danish, Danesh, John, Ingelsson, Erik, Ripatti, Samuli, Salomaa, Veikko, Erbel, Raimund, Joeckel, Karl-Heinz, Moebus, Susanne, Peters, Annette, Illig, Thomas, de Faire, Ulf, Hamsten, Anders, Morris, Andrew D., Donnelly, Peter J., Frayling, Timothy M., Hattersley, Andrew T., Boerwinkle, Eric, Melander, Olle, Kathiresan, Sekar, Nilsson, Peter M., Deloukas, Panos, Thorsteinsdottir, Unnur, Groop, Leif C., Stefansson, Kari, Hu, Frank, Pankow, James S., Dupuis, Josee, Meigs, James B., Altshuler, David, Boehnke, Michael, and McCarthy, Mark I.
- Abstract
To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
- Published
- 2012
- Full Text
- View/download PDF
50. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes
- Author
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Morris, Andrew P, Voight, Benjamin F, Teslovich, Tanya M, Ferreira, Teresa, Segrè, Ayellet V, Steinthorsdottir, Valgerdur, Strawbridge, Rona J, Khan, Abid Hassan, Grallert, Harald, Mahajan, Anubha, Prokopenko, Inga, Kang, Hyun Min, Dina, Christian, Esko, Tonu, Fraser, Ross M, Kanoni, Stavroula, Kumar, Ashish, Lagou, Vasiliki, Langenberg, Claudia, Luan, Jian'an, Lindgren, Cecilia M, Müller-Nurasyid, Martina, Pechlivanis, Sonali, Rayner, N William, Scott, Laura J, Wiltshire, Steven, Yengo, Loic, Kinnunen, Leena, Rossin, Elizabeth J, Raychaudhuri, Soumya, Johnson, Andrew D, Dimas, Antigone S, Loos, Ruth J F, Vedantam, Sailaja, Chen, Han, Florez, Jose C, Fox, Caroline, Liu, Ching-Ti, Rybin, Denis, Couper, David J, Kao, Wen Hong L, Li, Man, Cornelis, Marilyn C, Kraft, Peter, Sun, Qi, van Dam, Rob M, Stringham, Heather M, Jonsson, Anna Elisabet, Lind, Lars, Njølstad, Inger, Morris, Andrew P, Voight, Benjamin F, Teslovich, Tanya M, Ferreira, Teresa, Segrè, Ayellet V, Steinthorsdottir, Valgerdur, Strawbridge, Rona J, Khan, Abid Hassan, Grallert, Harald, Mahajan, Anubha, Prokopenko, Inga, Kang, Hyun Min, Dina, Christian, Esko, Tonu, Fraser, Ross M, Kanoni, Stavroula, Kumar, Ashish, Lagou, Vasiliki, Langenberg, Claudia, Luan, Jian'an, Lindgren, Cecilia M, Müller-Nurasyid, Martina, Pechlivanis, Sonali, Rayner, N William, Scott, Laura J, Wiltshire, Steven, Yengo, Loic, Kinnunen, Leena, Rossin, Elizabeth J, Raychaudhuri, Soumya, Johnson, Andrew D, Dimas, Antigone S, Loos, Ruth J F, Vedantam, Sailaja, Chen, Han, Florez, Jose C, Fox, Caroline, Liu, Ching-Ti, Rybin, Denis, Couper, David J, Kao, Wen Hong L, Li, Man, Cornelis, Marilyn C, Kraft, Peter, Sun, Qi, van Dam, Rob M, Stringham, Heather M, Jonsson, Anna Elisabet, Lind, Lars, and Njølstad, Inger
- Abstract
To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
- Published
- 2012
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