المؤلفون: Reyes-Osorio, Felipe, Garcia-Gaitan, Federico, Strachan, David J., Plechac, Petr, Clark, Stephen R., Nikolic, Branislav K.

مصطلحات موضوعية: Quantum Physics, Condensed Matter - Strongly Correlated Electrons, High Energy Physics - Theory, Mathematical Physics

الوصف: We develop a Schwinger-Keldysh field theory (SKFT) for open quantum systems interacting with a dissipative environment and apply it to the spin-boson model as an archetypical example where the environment is composed of a bosonic bath. Prior SKFT developments of this type have been confined to the Markovian regime, as an alternative to a conventional description by the Lindblad quantum master equation (QME) which is a time-local matrix differential equation. Here we combine SKFT with a two-particle irreducible (2PI) action that resums a class of Feynman diagrams to infinite order. We obtain the time-evolution of the spin density matrix in the form of a system of integro-differential equations applicable to both Markovian and non-Markovian regimes. The latter regime--where taking into account memory effects becomes essential--poses a challenge for standard methods when trying to incorporate arbitrary properties of the system, bath, and length of time evolution. The SKFT+2PI-computed time evolution of the spin expectation values in the Markovian regime reproduces the solution of the Lindblad QME, as long as the system-bath coupling in the latter is adjusted by increasing it. In the non-Markovian regime, SKFT+2PI yields a nonperturbative solution that mimics results from both hierarchical equations of motion and tensor networks methods that we employ as benchmarks. Our SKFT+2PI approach can also access challenging cases, such as zero-temperature and sub-Ohmic bath, as well as arbitrary long evolution times. Taking into account favorable numerical cost of solving the integro-differential equations with increasing number of spins, time steps or dimensionality the SKFT+2PI approach offers a promising route for simulation of driven-dissipative systems in quantum computing or quantum magnonics and spintronics in the presence of a variety of (single or multiple) dissipative environments.
Comment: 14 pages, 7 figures

الوصول الحر: http://arxiv.org/abs/2405.00765Test

المؤلفون: Keaton, Jacob, Kamali, Zoha, Xie, Tian, Vaez, Ahmad, Williams, Ariel, Goleva, Slavina, Ani, Alireza, Evangelou, Evangelos, Hellwege, Jacklyn, Yengo, Loic, Young, William, Traylor, Matthew, Giri, Ayush, Zheng, Zhili, Zeng, Jian, Chasman, Daniel, Morris, Andrew, Caulfield, Mark, Hwang, Shih-Jen, Kooner, Jaspal, Conen, David, Attia, John, Morrison, Alanna, Loos, Ruth, Kristiansson, Kati, Schmidt, Reinhold, Hicks, Andrew, Pramstaller, Peter, Nelson, Christopher, Samani, Nilesh, Risch, Lorenz, Gyllensten, Ulf, Melander, Olle, Riese, Harriette, Wilson, James, Campbell, Harry, Rich, Stephen, Psaty, Bruce, Lu, Yingchang, Guo, Xiuqing, Rice, Kenneth, Vollenweider, Peter, Sundström, Johan, Langenberg, Claudia, Tobin, Martin, Giedraitis, Vilmantas, Luan, Jianan, Tuomilehto, Jaakko, Kutalik, Zoltan, Ripatti, Samuli, Salomaa, Veikko, Girotto, Giorgia, Trompet, Stella, Jukema, J, van der Harst, Pim, Ridker, Paul, Giulianini, Franco, Vitart, Veronique, Goel, Anuj, Watkins, Hugh, Harris, Sarah, Deary, Ian, van der Most, Peter, Oldehinkel, Albertine, Keavney, Bernard, Hayward, Caroline, Campbell, Archie, Boehnke, Michael, Scott, Laura, Boutin, Thibaud, Mamasoula, Chrysovalanto, Järvelin, Marjo-Riitta, Peters, Annette, Gieger, Christian, Lakatta, Edward, Cucca, Francesco, Hui, Jennie, Knekt, Paul, Enroth, Stefan, De Borst, Martin, Polašek, Ozren, Concas, Maria, Catamo, Eulalia, Cocca, Massimiliano, Li-Gao, Ruifang, Hofer, Edith, Schmidt, Helena, Spedicati, Beatrice, Waldenberger, Melanie, Strachan, David, Laan, Maris, Teumer, Alexander, Dörr, Marcus, Gudnason, Vilmundur, Cook, James, Ruggiero, Daniela, Kolcic, Ivana, Boerwinkle, Eric, Traglia, Michela, Lehtimäki, Terho

المصدر: Nature Genetics. 56(5)

مصطلحات موضوعية: Female, Humans, Male, Blood Pressure, Genetic Predisposition to Disease, Genetic Risk Score, Genome-Wide Association Study, Hypertension, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors

الوصف: Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/0dj5c8rfTest

المؤلفون: Strachan, David J., Purkayastha, Archak, Clark, Stephen R.

مصطلحات موضوعية: Quantum Physics, Condensed Matter - Statistical Mechanics

الوصف: Since it's rediscovery in the twentieth century, the Mpemba effect, where a far-from-equilibrium state may relax faster than a state closer to equilibrium, has been extensively studied in classical systems and has recently received significant attention in quantum systems. Many theories explaining this counter-intuitive behavior in classical systems rely on memory effects. However, in quantum systems, the relation between the Mpemba effect and memory has remained unexplored. In this work, we consider a general non-Markovian open quantum setting and reveal new classes of quantum Mpemba effects, with no analog in Markovian quantum dynamics. Generically, open quantum dynamics possess a finite memory time and a unique steady state. Due to non-Markovian dynamics, even if the system is initialized in the steady state it can take a long time to relax back. We find other initial states that reach the steady state much faster. Most notably, we demonstrate that there can be an initial state in which the system reaches the steady state within the finite memory time itself, therefore giving the fastest possible relaxation to stationarity. We verify the effect for quantum dot systems coupled to electronic reservoirs in equilibrium and non-equilibrium setups at weak, intermediate and strong coupling, and both with and without interactions. Our work provides new insights into the rich physics underlying accelerated relaxation in quantum systems.
Comment: v2, 4 pages, 3 figures and supplemental material. Substantially updated from v1

الوصول الحر: http://arxiv.org/abs/2402.05756Test

المؤلفون: Rutter, Charlotte E, Silverwood, Richard J, Williams, Hywel C, Ellwood, Philippa, Asher, Innes, Garcia-Marcos, Luis, Strachan, David P, Pearce, Neil, Langan, Sinéad M, Chiarella, Pascual, ISAAC Phase Three Study Group

مرشدي الرسالة: Sinead.langan@lshtm.ac.uk

المصدر: Universidad Peruana de Ciencias Aplicadas (UPC)Repositorio Academico - UPCThe Journal of investigative dermatology.

مصطلحات موضوعية: Antibiotic agent, Paracetamol, Adolescent, Allergy, Article, Association, Asthma, Atopic dermatitis, Child, Cooking, Environmental exposure, Environmental factor, Female, Human, Major clinical study, Male, Prevalence, Priority journal, Risk factor, School, Symptom, Traffic

الوصف: Some previously described environmental associations for atopic eczema may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level results for multiple atopic eczema risk factors. The International Study of Asthma and Allergies in Childhood (i.e, ISAAC) Phase Three surveyed children in schools (the sampling unit) regarding atopic eczema symptoms and potential risk factors. We assessed the effect of these risk factors on atopic eczema symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence. Overall, 546,348 children from 53 countries were included. At ages 6–7 years, the strongest individual-level associations were with current paracetamol use (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.37–1.54), which persisted at school-level (OR = 1.55, 95% CI = 1.10–2.21), early-life antibiotics (OR = 1.41, 95% CI = 1.34–1.48), and early-life paracetamol use (OR = 1.28, 95% CI = 1.21–1.36), with the former persisting at the school level, whereas the latter was no longer observed (OR = 1.35, 95% CI = 1.00–1.82 and OR = 0.94, 95% CI = 0.69–1.28, respectively). At ages 13–14 years, the strongest associations at the individual level were with current paracetamol use (OR = 1.57, 95% CI = 1.51–1.63) and open-fire cooking (OR = 1.46, 95% CI = 1.33–1.62); both were stronger at the school level (OR = 2.57, 95% CI = 1.84–3.59 and OR = 2.38, 95% CI = 1.52–3.73, respectively). Association with exposure to heavy traffic (OR = 1.31, 95% CI = 1.27–1.36) also persisted at the school level (OR = 1.40, 95% CI = 1.07–1.82). Most individual- and school-level effects were consistent, tending to exclude reverse causation.
Revisión por pares

وصف الملف: application/pdf

العلاقة: https://www.ncbi.nlm.nih.gov/pubmed/30521836Test

الإتاحة: http://hdl.handle.net/10757/625720Test

المؤلفون: Silverwood, Richard J, Rutter, Charlotte E, Mitchell, Edwin A, Asher, M Innes, Garcia-Marcos, Luis, Strachan, David P, Pearce, Neil, Chiarella, Pascual, ISAAC Phase Three Study Group.

مرشدي الرسالة: neil.pearce@lshtm.ac.uk

المصدر: Universidad Peruana de Ciencias Aplicadas (UPC)Repositorio Academico - UPCClinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

مصطلحات موضوعية: asthma, environment and hygiene hypothesis, epidemiology

الوصف: Background: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global prevalence of symptoms of asthma in children. We undertook comprehensive analyses addressing risk factors for asthma symptoms in combination, at both the individual and the school level, to explore the potential role of reverse causation due to selective avoidance or confounding by indication. Objective: To explore the role of reverse causation in risk factors of asthma symptoms. Methods: We compared two sets of multilevel logistic regression analyses, using (a) individual level exposure data and (b) school level average exposure (ie prevalence), in two different age groups. In individual level analyses, reverse causation is a possible concern if individual level exposure statuses were changed as a result of asthma symptoms or diagnosis. School level analyses may suffer from ecologic confounding, but reverse causation is less of a concern because individual changes in exposure status as a result of asthma symptoms would only have a small effect on overall school exposure levels. Results: There were 131 924 children aged 6-7 years (2428 schools, 25 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (odds ratio = 2.06; 95% confidence interval 1.97-2.16), early life antibiotic use (1.65; 1.58-1.73) and open fire cooking (1.44; 1.26-1.65). In school level analyses, these risk factors again showed increased risks. There were 238 586 adolescents aged 13-14 years (2072 schools, 42 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (1.80; 1.75-1.86), cooking on an open fire (1.32; 1.22-1.43) and maternal tobacco use (1.23; 1.18-1.27). In school level analyses, these risk factors again showed increased risks. Conclusions & clinical relevance: These analyses strengthen the potentially causal interpretation of previously reported individual level findings, by providing evidence against reverse causation.
Revisión por pares

وصف الملف: application/pdf

العلاقة: https://www.ncbi.nlm.nih.gov/pubmed/30508327Test

الإتاحة: http://hdl.handle.net/10757/625721Test

المؤلفون: Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian'an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O'Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Ismail, Said I., Al-Muftah, Wadha, Badji, Radja, Mbarek, Hamdi, Darwish, Dima, Fadl, Tasnim, Yasin, Heba, Ennaifar, Maryem, Abdellatif, Rania, Alkuwari, Fatima, Alvi, Muhammad, Al-Sarraj, Yasser, Saad, Chadi, Althani, Asmaa, Fethnou, Eleni, Qafoud, Fatima, Alkhayat, Eiman, Afifi, Nahla, Tomei, Sara, Liu, Wei, Lorenz, Stephan, Syed, Najeeb, Almabrazi, Hakeem, Vempalli, Fazulur Rehaman, Temanni, Ramzi, Abu Saqri, Tariq, Khatib, Mohammedhusen, Hamza, Mehshad, Abu Zaid, Tariq, El Khouly, Ahmed, Pathare, Tushar, Poolat, Shafeeq, Al-Ali, Rashid, Al-Khodor, Souhaila, Alshafai, Mashael, Badii, Ramin, Chouchane, Lotfi, Estivill, Xavier, Fakhro, Khalid, Mokrab, Younes, Puthen, Jithesh, V, Tatari, Zohreh, Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimaki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietilainen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josee, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., Tobin, Martin

المصدر: Nature Genetics. 55(3):410-422

الوصف: Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-509448Test
https://doi.org/10.1038/s41588-023-01314-0Test
https://uu.diva-portal.org/smash/get/diva2:1789381/FULLTEXT01.pdfTest

المؤلفون: Juhász, Péter, Krstajić, Milan, Strachan, David, Gandar, Edward, Smith, Robert P.

المصدر: Phys. Rev. A 105, L061301 (2022)

مصطلحات موضوعية: Condensed Matter - Quantum Gases

الوصف: Homogeneous quantum gases open up new possibilities for studying many-body phenomena and have now been realised for a variety of systems. For gases with short-range interactions the way to make the cloud homogeneous is, predictably, to trap it in an ideal (homogeneous) box potential. We show that creating a close to homogeneous dipolar gas in the roton regime, when long-range interactions are important, actually requires trapping particles in soft-walled (inhomogeneous) box-like potentials. In particular, we numerically explore a dipolar gas confined in a pancake trap which is harmonic along the polarisation axis and a cylindrically symmetric power-law potential $r^p$ radially. We find that intermediate $p$'s maximise the proportion of the sample that can be brought close to the critical density required to reach the roton regime, whereas higher $p$'s trigger density oscillations near the wall even when the bulk of the system is not in the roton regime. We characterise how the optimum density distribution depends on the shape of the trapping potential and find it is controlled by the trap wall steepness.
Comment: 7 pages, 3 figures

الوصول الحر: http://arxiv.org/abs/2112.12737Test

المؤلفون: Temprano‐Sagrera, Gerard, Sitlani, Colleen M, Bone, William P, Martin‐Bornez, Miguel, Voight, Benjamin F, Morrison, Alanna C, Damrauer, Scott M, de Vries, Paul S, Smith, Nicholas L, Sabater‐Lleal, Maria, Dehghan, Abbas, Heath, Adam S, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward‐Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook‐Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank WG, Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, Jhun, Min‐A, Chen, Ming‐Huei, de Maat, Moniek PM, Pankratz, Nathan, Peyser, Patricia A, Elliot, Paul, Wei, Peng, Wild, Philipp S, Morange, Pierre E, van der Harst, Pim, Yang, Qiong, Le, Ngoc‐Quynh, Marioni, Riccardo, Li, Ruifang, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J Wouter, Guo, Xiuqing, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K

المصدر: Journal of Thrombosis and Haemostasis. 20(6)

مصطلحات موضوعية: Genetics, Biotechnology, Human Genome, Atherosclerosis, Prevention, Cardiovascular, Hematology, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular Diseases, Factor XI, Genetic Predisposition to Disease, Genome-Wide Association Study, Hemostasis, Hemostatics, Humans, Phenotype, Polymorphism, Single Nucleotide, Tissue Plasminogen Activator, blood coagulation, cardiovascular diseases, genetic pleiotropy, genome-wide association study, hemostasis, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology

الوصف: BackgroundMulti-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes.ObjectivesTo discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events.MethodsSummary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10-9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27).ResultsAcross the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes.ConclusionsThe discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2wd699zzTest

المؤلفون: Keaton, Jacob M, Kamali, Zoha, Xie, Tian, Vaez, Ahmad, Williams, Ariel, Goleva, Slavina B, Ani, Alireza, Evangelou, Evangelos, Hellwege, Jacklyn N, Yengo, Loic, Young, William J, Traylor, Matthew, Giri, Ayush, Zheng, Zhili, Zeng, Jian, Chasman, Daniel I, Morris, Andrew P, Caulfield, Mark J, Hwang, Shih-Jen, Kooner, Jaspal S, Conen, David, Attia, John R, Morrison, Alanna C, Loos, Ruth JF, Kristiansson, Kati, Schmidt, Reinhold, Hicks, Andrew A, Pramstaller, Peter P, Nelson, Christopher P, Samani, Nilesh J, Risch, Lorenz, Gyllensten, Ulf, Melander, Olle, Riese, Harriette, Wilson, James F, Campbell, Harry, Rich, Stephen S, Psaty, Bruce M, Lu, Yingchang, Rotter, Jerome I, Guo, Xiuqing, Rice, Kenneth M, Vollenweider, Peter, Sundström, Johan, Langenberg, Claudia, Tobin, Martin D, Giedraitis, Vilmantas, Luan, Jian'an, Tuomilehto, Jaakko, Kutalik, Zoltan, Ripatti, Samuli, Salomaa, Veikko, Girotto, Giorgia, Trompet, Stella, Jukema, J Wouter, van der Harst, Pim, Ridker, Paul M, Giulianini, Franco, Vitart, Veronique, Goel, Anuj, Watkins, Hugh, Harris, Sarah E, Deary, Ian J, van der Most, Peter J, Oldehinkel, Albertine J, Keavney, Bernard D, Hayward, Caroline, Campbell, Archie, Boehnke, Michael, Scott, Laura J, Boutin, Thibaud, Mamasoula, Chrysovalanto, Järvelin, Marjo-Riitta, Peters, Annette, Gieger, Christian, Lakatta, Edward G, Cucca, Francesco, Hui, Jennie, Knekt, Paul, Enroth, Stefan, De Borst, Martin H, Polašek, Ozren, Concas, Maria Pina, Catamo, Eulalia, Cocca, Massimiliano, Li-Gao, Ruifang, Hofer, Edith, Schmidt, Helena, Spedicati, Beatrice, Waldenberger, Melanie, Strachan, David P, Laan, Maris, Teumer, Alexander, Dörr, Marcus, Gudnason, Vilmundur, Cook, James P, Ruggiero, Daniela, Kolcic, Ivana, Boerwinkle, Eric, Traglia, Michela, Lehtimäki, Terho, Raitakari, Olli T, Johnson, Andrew D, Newton-Cheh, Christopher, Brown, Morris J, Dominiczak, Anna F, Sever, Peter J, Poulter, Neil, Chambers, John C, Elosua, Roberto, Siscovick, David, Esko, Tõnu, Metspalu, Andres, Strawbridge, Rona J, Laakso, Markku, Hamsten, Anders, Hottenga, Jouke-Jan, de Geus, Eco, Morris, Andrew D, Palmer, Colin NA, Nolte, Ilja M, Milaneschi, Yuri, Marten, Jonathan, Wright, Alan, Zeggini, Eleftheria, Howson, Joanna MM, O'Donnell, Christopher J, Spector, Tim, Nalls, Mike A, Simonsick, Eleanor M, Liu, Yongmei, van Duijn, Cornelia M, Butterworth, Adam S, Danesh, John N, Menni, Cristina, Wareham, Nicholas J, Khaw, Kay-Tee, Sun, Yan V, Wilson, Peter WF, Cho, Kelly, Visscher, Peter M, Denny, Joshua C, Million Veteran Program, Lifelines Cohort Study, CHARGE consortium, ICBP Consortium, Levy, Daniel, Edwards, Todd L, Munroe, Patricia B, Snieder, Harold, Warren, Helen R

مصطلحات موضوعية: Female, Humans, Male, Blood Pressure, Genetic Predisposition to Disease, Genetic Risk Score, Genome-Wide Association Study, Hypertension, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors

الوصف: Acknowledgements: J.N.H. is supported by the National Institutes of Health (grant no. K12HD04348; principal investigator K. E. Hartmann). T.E. and A.M. were supported by the Council of Europe (grant no. 2014-2020.4.01.15-0012) and Estonian Research Council (grant no. PRG1291). Z.K. is supported by Isfahan University of Medical Sciences (3400581) and Iran’s National Elites Foundation (grant no. ISF140100108). J.N.D. holds a British Heart Foundation Professorship and a National Institute for Health Research Senior Investigator Award. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Cohort support was provided by the Million Veteran Program (MVP) VA Award BX004821 (to P.W.F.W. and K.C.). Individual cohort acknowledgements are provided in the Supplementary Notes. We dedicate this paper to the memory of Evangelos Evangelou (the first author of our previous BP-GWAS paper5), who sadly passed away in July 2023. ; Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in ...

وصف الملف: application/pdf; application/zip; text/xml

العلاقة: https://www.repository.cam.ac.uk/handle/1810/368419Test

الإتاحة: https://www.repository.cam.ac.uk/handle/1810/368419Test

المؤلفون: Early Growth Genetics Consortium, Bradfield, Jonathan P., Kember, Rachel L., Ulrich, Anna, Balkiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M., Bell, Joshua A., Broadaway, K. Alaine, Chen, Zhanghua, Chai, Jin Fang, Davies, Neil M., Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M., Have, Christian Theil, Strachan, David P., Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H., Wang, Carol A., Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithioff-Bøjsøe, Christine, Gauderman, W. James, Glessner, Joseph T., Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L., Kähönen, Mika, Mononen, Nina, Eriksson, Johan G., Lehtimäki, Terho, Mykkänen, Juha, Shepherd, John A.

المساهمون: Tampere University, Internal and Respiratory medicine & Critical care, Skin & Allergy, Clinical physiology and nuclear medicine, Children’s and Women’s health, Diagnostic Medicine, Psychiatry, Department of Clinical Chemistry

مصطلحات موضوعية: 3121 Internal medicine

الوصف: BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern. ; Peer reviewed

وصف الملف: fulltext

العلاقة: 22; 25; ORCID: /0000-0002-2555-4427/work/153554979; ORCID: /0000-0002-4510-7341/work/153555363; https://trepo.tuni.fi/handle/10024/155052Test; URN:NBN:fi:tuni-202402192333

الإتاحة: https://doi.org/10.1186/s13059-023-03136-zTest
https://trepo.tuni.fi/handle/10024/155052Test