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3. How is model-related uncertainty quantified and reported in different disciplines?

Author

Simmonds, Emily G., Adjei, Kwaku Peprah, Andersen, Christoffer Wold, Aspheim, Janne Cathrin Hetle, Battistin, Claudia, Bulso, Nicola, Christensen, Hannah, Cretois, Benjamin, Cubero, Ryan, Davidovich, Ivan A., Dickel, Lisa, Dunn, Benjamin, Dunn-Sigouin, Etienne, Dyrstad, Karin, Einum, Sigurd, Giglio, Donata, Gjerlow, Haakon, Godefroidt, Amelie, Gonzalez-Gil, Ricardo, Cogno, Soledad Gonzalo, Grosse, Fabian, Halloran, Paul, Jensen, Mari F., Kennedy, John James, Langsaether, Peter Egge, Laverick, Jack H., Lederberger, Debora, Li, Camille, Mandeville, Elizabeth, Mandeville, Caitlin, Moe, Espen, Schroder, Tobias Navarro, Nunan, David, Parada, Jorge Sicacha, Simpson, Melanie Rae, Skarstein, Emma Sofie, Spensberger, Clemens, Stevens, Richard, Subramanian, Aneesh, Svendsen, Lea, Theisen, Ole Magnus, Watret, Connor, and OHara, Robert B.

Subjects
Statistics - Applications, Physics - Atmospheric and Oceanic Physics, Quantitative Biology - Quantitative Methods
Abstract

How do we know how much we know? Quantifying uncertainty associated with our modelling work is the only way we can answer how much we know about any phenomenon. With quantitative science now highly influential in the public sphere and the results from models translating into action, we must support our conclusions with sufficient rigour to produce useful, reproducible results. Incomplete consideration of model-based uncertainties can lead to false conclusions with real world impacts. Despite these potentially damaging consequences, uncertainty consideration is incomplete both within and across scientific fields. We take a unique interdisciplinary approach and conduct a systematic audit of model-related uncertainty quantification from seven scientific fields, spanning the biological, physical, and social sciences. Our results show no single field is achieving complete consideration of model uncertainties, but together we can fill the gaps. We propose opportunities to improve the quantification of uncertainty through use of a source framework for uncertainty consideration, model type specific guidelines, improved presentation, and shared best practice. We also identify shared outstanding challenges (uncertainty in input data, balancing trade-offs, error propagation, and defining how much uncertainty is required). Finally, we make nine concrete recommendations for current practice (following good practice guidelines and an uncertainty checklist, presenting uncertainty numerically, and propagating model-related uncertainty into conclusions), future research priorities (uncertainty in input data, quantifying uncertainty in complex models, and the importance of missing uncertainty in different contexts), and general research standards across the sciences (transparency about study limitations and dedicated uncertainty sections of manuscripts)., Comment: 40 Pages (including supporting information), 3 Figures, 2 Boxes, 1 Table

Published
2022
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4. Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial

Author

Austin, David, Maier, Rebecca H., Akhter, Nasima, Sayari, Mohammad, Ogundimu, Emmanuel, Maddox, Jamie M., Vahabi, Sharareh, Humphreys, Alison C., Graham, Janine, Oxenham, Helen, Haney, Sophie, Cresti, Nicola, Verrill, Mark, Osborne, Wendy, Wright, Kathryn L., Goranova, Rebecca, Bailey, James R., Kalakonda, Nagesh, Macheta, Mac, Kilner, Mari F., Young, Moya E., Morley, Nick J., Neelakantan, Pratap, Gilbert, Georgia, Thomas, Byju K., Graham, Richard J., Fujisawa, Takeshi, Mills, Nicholas L., Hildreth, Victoria, Prichard, Jonathan, Kasim, Adetayo S., Hancock, Helen C., and Plummer, Chris

Published
2024
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6. Parallel Statistical Model Checking for Safety Verification in Smart Grids

Author

Mancini, T., Mari, F., Melatti, I., Salvo, I., Tronci, E., Gruber, J. K., Hayes, B., Prodanovic, M., and Elmegaard, L.

Subjects
Electrical Engineering and Systems Science - Systems and Control, Computer Science - Distributed, Parallel, and Cluster Computing, 68Q60, I.6.3, J.2
Abstract

By using small computing devices deployed at user premises, Autonomous Demand Response (ADR) adapts users electricity consumption to given time-dependent electricity tariffs. This allows end-users to save on their electricity bill and Distribution System Operators to optimise (through suitable time-dependent tariffs) management of the electric grid by avoiding demand peaks. Unfortunately, even with ADR, users power consumption may deviate from the expected (minimum cost) one, e.g., because ADR devices fail to correctly forecast energy needs at user premises. As a result, the aggregated power demand may present undesirable peaks. In this paper we address such a problem by presenting methods and a software tool (APD-Analyser) implementing them, enabling Distribution System Operators to effectively verify that a given time-dependent electricity tariff achieves the desired goals even when end-users deviate from their expected behaviour. We show feasibility of the proposed approach through a realistic scenario from a medium voltage Danish distribution network., Comment: 6 pages, 1 figure. In SmartGridComm 2018. IEEE, 2018

Published
2021
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7. Risk factors and healthcare costs associated with long bone fracture non-union: a retrospective US claims database analysis

Author

Mari F. Vanderkarr, Jill W. Ruppenkamp, Mollie Vanderkarr, Chantal E. Holy, and Michael Blauth

Subjects
Fractures, Non-union, Risk factors, Bone fractures, Cost analysis, Orthopedic surgery, RD701-811, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background Few contemporary US-based long bone non-union analyses have recently been published. Our study was designed to provide a current understanding of non-union risks and costs, from the payers' perspective. Methods The Merative™ MarketScan® Commercial Claims and Encounters database was used. Patients with surgically treated long bone (femur, tibia, or humerus) fractures in the inpatient setting, from Q4 2015 to most recent, were identified. Exclusion criteria included polytrauma and amputation at index. The primary outcome was a diagnosis of non-union in the 12 and 24 months post-index. Additional outcomes included concurrent infection, reoperation, and total healthcare costs. Age, gender, comorbidities, fracture characteristics, and severity were identified for all patients. Descriptive analyses were performed. Crude and adjusted rates of non-union (using Poisson regressions with log link) were calculated. Marginal incremental cost of care associated with non-union and infected non-union and reoperation were estimated using a generalized linear model with log link and gamma distribution. Results A total of 12,770, 13,504, and 4,805 patients with femoral, tibial, or humeral surgically treated fractures were identified, 74–89% were displaced, and 18–27% were comminuted. Two-year rates of non-union reached 8.5% (8.0%–9.1%), 9.1% (8.6%–9.7%), and 7.2% (6.4%–8.1%) in the femoral, tibial, and humeral fracture cohorts, respectively. Shaft fractures were at increased risk of non-union versus fractures in other sites (risk ratio (RR) in shaft fractures of the femur: 2.36 (1.81–3.04); tibia: 1.95 (1.47–2.57); humerus: 2.02 (1.42–2.87)). Fractures with severe soft tissue trauma (open vs. closed, Gustilo III vs. Gustilo I–II) were also at increased risk for non-union (RR for Gustilo III fracture (vs. closed) for femur: R = 1.96 (1.45–2.58), for tibia: 3.33 (2.85–3.87), RR for open (vs. closed) for humerus: 1.74 (1.30–2.32)). For all fractures, younger patients had a reduced risk of non-union compared to older patients. For tibial fractures, increasing comorbidity (Elixhauser Index 5 or greater) was associated with an increased risk of non-union. The two-year marginal cost of non-union ranged from $33K-$45K. Non-union reoperation added $16K–$34K in incremental costs. Concurrent infection further increased costs by $46K–$86K. Conclusions Non-union affects 7–10% of surgically treated long bone fracture cases. Shaft and complex fractures were at increased risk for non-union.

Published
2023
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8. Continuous Wavelet Frames on the Sphere: The Group-Theoretic Approach Revisited

Author

Dahlke, S., De Mari, F., De Vito, E., Hansen, M., Hasannasab, M., Quellmalz, M., Steidl, G., and Teschke, G.

Subjects
Mathematics - Functional Analysis
Abstract

In \cite{AV99}, Antoine and Vandergheynst propose a group-theoretic approach to continuous wavelet frames on the sphere. The frame is constructed from a single so-called admissible function by applying the unitary operators associated to a representation of the Lorentz group, which is square-integrable modulo the nilpotent factor of the Iwasawa decomposition. We prove necessary and sufficient conditions for functions on the sphere, which ensure that the corresponding system is a frame. We strengthen a similar result in \cite{AV99} by providing a complete and detailed proof.

Published
2020
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10. ARID1B-related disorder in 87 adults: Natural history and self-sustainability

Author

van der Sluijs, P.J., Gösgens, M., Dingemans, A.J.M., Striano, P., Riva, A., Mignot, C., Faudet, A., Vasileiou, G., Walther, M., Schrier Vergano, S.A., Alders, M., Alkuraya, F.S., Alorainy, I., Alsaif, H.S., Anderlid, B., Bache, I., van Beek, I., Blanluet, M., van Bon, B.W., Brunet, T., Brunner, H., Carriero, M.L., Charles, P., Chatron, N., Coccia, E., Dubourg, C., Earl, R.K., Eichler, E.E., Faivre, L., Foulds, N., Graziano, C., Guerrot, A.M., Hashem, M.O., Heide, S., Heron, D., Hickey, S.E., Hopman, S.M.J., Kattentidt-Mouravieva, A., Kerkhof, J., Klein Wassink-Ruiter, J.S., Kurtz-Nelson, E.C., Kušíková, K., Kvarnung, M., Lecoquierre, F., Leszinski, G.S., Loberti, L., Magoulas, P.L., Mari, F., Maystadt, I., Merla, G., Milunsky, J.M., Moortgat, S., Nicolas, G., Leary, M.O.’, Odent, S., Ozmore, J.R., Parbhoo, K., Pfundt, R., Piccione, M., Pinto, A.M., Popp, B., Putoux, A., Rehm, H.L., Reis, A., Renieri, A., Rosenfeld, J.A., Rossi, M., Salzano, E., Saugier-Veber, P., Seri, M., Severi, G., Sonmez, F.M., Strobl-Wildemann, G., Stuurman, K.E., Uctepe, E., Van Esch, H., Vitetta, G., de Vries, B.B.A., Wahl, D., Wang, T., Zacher, P., Heitink, K.R., Ropers, F.G., Steenbeek, D., Rybak, T., and Santen, G.W.E.

Published
2024
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11. The predictive and prognostic value of weight loss and body composition prior to and during immune checkpoint inhibition in recurrent or metastatic head and neck cancer patients

Author

Anna C. H. Willemsen, Nina De Moor, Jeroen Van Dessel, Laura W. J. Baijens, Michel Bila, Esther Hauben, Mari F. C. M. van denHout, Vincent Vander Poorten, Ann Hoeben, Paul M. Clement, and Annemie M. W. J. Schols

Subjects
body composition, cachexia, head and neck cancer, immune checkpoint inhibitors, weight loss, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Response rates of immune checkpoint inhibitor (ICI) therapy for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are low. Patients and Methods This retrospective multicentre cohort study evaluates the predictive and prognostic value of weight loss and changes in body composition prior and during therapy. Patient, tumor, and treatment characteristics of 98 patients were retrieved, including neutrophil and platelet‐lymphocyte‐ratio (NLR and PLR). Programmed death‐ligand 1 (PD‐L1) expression was determined on residual material. Cachexia was defined according to Fearon et al. (2011). Skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were evaluated on computed tomography scans at the third lumbar vertebrae level. Univariable and multivariable regression analyses were performed for 6 months progression free survival (PFS6m) and overall survival (OS). Results Significant early weight loss (>2%) during the first 6 weeks of therapy was shown in 34 patients (35%). This patient subgroup had a significantly higher NLR and PLR at baseline. NLR and PLR were inversely correlated with SM and VAT index. Independent predictors of PFS6m were lower World Health Organization performance status (HR 0.16 [0.04–0.54] p = 0.003), higher baseline SAT index (HR 1.045 [1.02–1.08] p = 0.003), and weight loss 2% early weight loss remained a predictor of OS, independent of PD‐L1 expression (HR 2.09 [1.11–3.92] p = 0.02, HR 2.18 [1.13–4.21] p = 0.02). Conclusion We conclude that the combination of cachexia at baseline and weight loss during ICI therapy is associated with worse OS in R/M HNSCC patients, independent of PD‐L1 expression.

Published
2023
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13. Incidence, costs and post-operative complications following ankle fracture – A US claims database analysis

Author

Mari F. Vanderkarr, Jill W. Ruppenkamp, Mollie Vanderkarr, Anjani Parikh, Chantal E. Holy, and Matthew Putnam

Subjects
Ankle fractures, Comorbidities, Complications, Costs, Payments, Claims database, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background The epidemiology and payer costs for ankle fractures are not well documented. This study evaluated: (1) the incidence of ankle fracture and ankle surgery following fracture in the US population; and (2) the clinical presentation of patients presenting with ankle fractures requiring surgery, their complication rates, and payer costs. Methods Patients in the IBM® MarketScan® Commercial and Medicare Supplemental databases with an inpatient/outpatient diagnosis of ankle fracture from 2016 to 2019 were stratified by age group and gender, and rates of fracture per 10,000 enrollees were estimated. Surgically-treated patients between January 2016 – October 2021 were further analyzed. One-year post-surgical outcomes evaluated complication rates (e.g., infection, residual pain), reoperations, and 1-year payments. Standard descriptive statistics were calculated for all variables and outcomes. Generalized linear models were designed to estimate payments for surgical care and incremental payments associated with postoperative complications. Results Fracture cases affected 0.14% of the population; 23.4% of fractures required surgery. Pediatric and elderly patients were at increased risk. From 3 weeks to 12 months following index ankle surgery, 5.5% (5.3% - 5.7%) of commercially insured and 5.9% (5.1% - 6.8%) of Medicare patients required a new surgery. Infection was observed in 4.4% (4.2% - 4.6%) commercially insured and 9.8% (8.8% - 10.9%) Medicare patients, and residual pain 3 months post-surgery was observed in 29.5% (28.7% - 30.3%) commercially-insured and 39.3% (36.0% - 42.6%) Medicare patients. Commercial payments for index surgery ranged from $9,821 (95% CI: $9,697 - $9,945) in the ambulatory surgical center to $28,169 (95% CI: $27,780 - $28,559) in the hospital inpatient setting, and from $16,775 (95% CI: $16,668 - $16,882) in patients with closed fractures, to $41,206 (95% CI: $38,795 - $43,617) in patients with Gustilo III fractures. Incremental commercial payments for pain and infection averaged $5,200 (95% CI: $4,261 - $6,139) and $27,510 (95% CI: $21,759 - $33,261), respectively. Conclusion Ankle fracture has a high incidence and complication rate. Residual pain affects more than one-third of all patients. Ankle fracture thus presents a significant societal impact in terms of patient outcomes and payer burden.

Published
2022
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15. Insights into the quantification and reporting of model-related uncertainty across different disciplines

Author

Simmonds, Emily G., Adjei, Kwaku Peprah, Andersen, Christoffer Wold, Hetle Aspheim, Janne Cathrin, Battistin, Claudia, Bulso, Nicola, Christensen, Hannah M., Cretois, Benjamin, Cubero, Ryan, Davidovich, Iván A., Dickel, Lisa, Dunn, Benjamin, Dunn-Sigouin, Etienne, Dyrstad, Karin, Einum, Sigurd, Giglio, Donata, Gjerløw, Haakon, Godefroidt, Amélie, González-Gil, Ricardo, Gonzalo Cogno, Soledad, Große, Fabian, Halloran, Paul, Jensen, Mari F., Kennedy, John James, Langsæther, Peter Egge, Laverick, Jack H., Lederberger, Debora, Li, Camille, Mandeville, Elizabeth G., Mandeville, Caitlin, Moe, Espen, Navarro Schröder, Tobias, Nunan, David, Sicacha-Parada, Jorge, Simpson, Melanie Rae, Skarstein, Emma Sofie, Spensberger, Clemens, Stevens, Richard, Subramanian, Aneesh C., Svendsen, Lea, Theisen, Ole Magnus, Watret, Connor, and O’Hara, Robert B.

Published
2022
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18. Odontogenic Myxomas Harbor Recurrent Copy Number Alterations and a Distinct Methylation Signature.

Author

Kleijn, Tony G., Ameline, Baptiste, Schreuder, Willem H., Kooistra, Wierd, Doff, Jan J., Witjes, Max, Pichardo, Sarina E. C., Lausová, Tereza, Koppes, Sjors A., van den Hout, Mari F. C. M., van Engen-van Grunsven, Ilse C. H., Flucke, Uta E., de Lange, Jan, Szuhai, Karoly, Briaire-de Bruijn, Inge H., Savci-Heijink, Dilara C., Suurmeijer, Albert J. H., Bovée, Judith V. M. G., von Deimling, Andreas, and Baumhoer, Daniel

Published
2024
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20. Insights into the quantification and reporting of model-related uncertainty across different disciplines

Author

Emily G. Simmonds, Kwaku Peprah Adjei, Christoffer Wold Andersen, Janne Cathrin Hetle Aspheim, Claudia Battistin, Nicola Bulso, Hannah M. Christensen, Benjamin Cretois, Ryan Cubero, Iván A. Davidovich, Lisa Dickel, Benjamin Dunn, Etienne Dunn-Sigouin, Karin Dyrstad, Sigurd Einum, Donata Giglio, Haakon Gjerløw, Amélie Godefroidt, Ricardo González-Gil, Soledad Gonzalo Cogno, Fabian Große, Paul Halloran, Mari F. Jensen, John James Kennedy, Peter Egge Langsæther, Jack H. Laverick, Debora Lederberger, Camille Li, Elizabeth G. Mandeville, Caitlin Mandeville, Espen Moe, Tobias Navarro Schröder, David Nunan, Jorge Sicacha-Parada, Melanie Rae Simpson, Emma Sofie Skarstein, Clemens Spensberger, Richard Stevens, Aneesh C. Subramanian, Lea Svendsen, Ole Magnus Theisen, Connor Watret, and Robert B. O’Hara

Subjects
Statistical physics, Science
Abstract

Summary: Quantifying uncertainty associated with our models is the only way we can express how much we know about any phenomenon. Incomplete consideration of model-based uncertainties can lead to overstated conclusions with real-world impacts in diverse spheres, including conservation, epidemiology, climate science, and policy. Despite these potentially damaging consequences, we still know little about how different fields quantify and report uncertainty. We introduce the “sources of uncertainty” framework, using it to conduct a systematic audit of model-related uncertainty quantification from seven scientific fields, spanning the biological, physical, and political sciences. Our interdisciplinary audit shows no field fully considers all possible sources of uncertainty, but each has its own best practices alongside shared outstanding challenges. We make ten easy-to-implement recommendations to improve the consistency, completeness, and clarity of reporting on model-related uncertainty. These recommendations serve as a guide to best practices across scientific fields and expand our toolbox for high-quality research.

Published
2022
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21. Shifts in Greenland interannual climate variability lead Dansgaard-Oeschger abrupt warming by hundreds of years

Author

Brashear, Chloe A., primary, Jones, Tyler R., additional, Morris, Valerie, additional, Vaughn, Bruce H., additional, Roberts, William H. G., additional, Skorski, William B., additional, Hughes, Abigail G., additional, Nunn, Richard, additional, Rasmussen, Sune Olander, additional, Cuffey, Kurt M., additional, Vinther, Bo M., additional, Sowers, Todd, additional, Buizert, Christo, additional, Gkinis, Vasileios, additional, Holme, Christian, additional, Jensen, Mari F., additional, Kjellman, Sofia E., additional, Langebroek, Petra M., additional, Mekhaldi, Florian, additional, Rozmiarek, Kevin S., additional, Rheinlænder, Jonathan W., additional, Simon, Margit, additional, Sinnl, Giulia, additional, Smith-Johnsen, Silje, additional, and White, James W. C., additional

Published
2024
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25. Proximity ligation‐based sequencing for the identification of human papillomavirus genomic integration sites in formalin‐fixed paraffin embedded oropharyngeal squamous cell carcinomas.

Author

Demers, Imke, Balaji, Harini, Feitsma, Harma, Stelloo, Ellen, Swennenhuis, Joost, Sergeeva, Irina, Wuerdemann, Nora, van den Hout, Mari F. C. M., Wagner, Steffen, Kremer, Bernd, Klussmann, Jens P., Huebbers, Christian U., and Speel, Ernst‐Jan M.

Subjects
HUMAN papillomavirus, CHROMOSOMAL rearrangement, VIRAL genomes, POLYMERASE chain reaction, SQUAMOUS cell carcinoma
Abstract

Human papillomavirus (HPV) infections are an increasing cause of oropharyngeal squamous cell carcinomas (OPSCC). Integration of the viral genome into the host genome is suggested to affect carcinogenesis, however, the correlation with OPSCC patient prognosis is still unclear. Research on HPV integration is hampered by current integration detection technologies and their unsuitability for formalin‐fixed paraffin‐embedded (FFPE) tissues. This study aims to develop and validate a novel targeted proximity‐ligation based sequencing method (targeted locus amplification/capture [TLA/TLC]) for HPV integration detection in cell lines and FFPE OPSCCs. For the identification of HPV integrations, TLA/TLC was applied to 7 cell lines and 27 FFPE OPSCCs. Following preprocessing steps, a polymerase chain reaction (PCR)‐based HPV enrichment was performed on the cell lines and a capture‐based HPV enrichment was performed on the FFPE tissues before paired‐end sequencing. TLA was able to sequence up to hundreds of kb around the target, detecting exact HPV integration loci, structural variants, and chromosomal rearrangements. In all cell lines, one or more integration sites were identified, in accordance with detection of integrated papillomavirus sequences PCR data and the literature. TLC detected integrated HPV in 15/27 FFPE OPSCCs and identified simple and complex integration patterns. In general, TLA/TLC confirmed PCR data and detected additional integration sites. In conclusion TLA/TLC reliably and robustly detects HPV integration in cell lines and FFPE OPSCCs, enabling large, population‐based studies on the clinical relevance of HPV integration. Furthermore, this approach might be valuable for clonality assessment of HPV‐related tumors in clinical diagnostics. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Abdominal inflammatory myofibroblastic tumour: Clinicopathological and molecular analysis of 20 cases, highlighting potential therapeutic targets.

Author

Vernemmen, Astrid I P, Samarska, Iryna V, Speel, Ernst‐Jan M, Riedl, Robert G, Goudkade, Danny, de Bruïne, Adriaan P, Wouda, Siep, van Marion, Arienne M, Verlinden, Ivana V, van Lijnschoten, Ineke, Friederich, Pieter, Winnepenninckx, Véronique J L, zur Hausen, Axel, Sciot, Raf M E, and van den Hout, Mari F C M

Subjects
DRUG target, ANAPLASTIC lymphoma kinase, DNA analysis, GENE fusion, RNA analysis, PROTEIN-tyrosine kinases
Abstract

Aims: Inflammatory myofibroblastic tumour (IMT) is a rare mesenchymal neoplasm of intermediate malignant potential, occurring at any age and at multiple sites. Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of IMT, typically involving the abdomen. Most IMTs harbour kinase gene fusions, especially involving ALK and ROS1, but 20–30% of IMTs show no detectable translocations. The aim of this study is to further delineate clinicopathological and molecular characteristics of abdominal IMT and discover potential new therapeutic targets. Methods and results: In 20 IMTs, including four EIMS, RNA fusion analysis was performed, followed by multiplex DNA analysis if no ALK or ROS1 fusion was detected. Fourteen IMTs (70.0%) had an ALK translocation and the fusion partner was identified in 11, including a RRBP1::ALK fusion, not previously described in classical (non‐EIMS) IMT. RANBP2::ALK fusion was demonstrated in all EIMS. One IMT had a ROS1 fusion. In all ALK/ROS1 translocation‐negative IMTs mutations or fusions – as yet unreported in primary IMT – were found in genes related to the receptor tyrosine kinase (RTK)/PI3K/AKT pathway. Three of four patients with EIMS died of disease [mean survival 8 months (4–15 months)], whereas only one of 14 classical IMT patients succumbed to disease [mean follow‐up time 52 months (2–204 months); P < 0.01]. Conclusion: This study shows the wide clinical spectrum of abdominal IMTs and affirms the poor prognosis of EIMS, raising discussion about its status as IMT subtype. Furthermore, the newly detected alterations of the RTK/PI3K/AKT pathway expand the molecular landscape of IMTs and provide potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Information in Healthcare - From Data to Knowledge: Improving Data Literacy Competencies.

Author

EGBERT, Nicole, HAUKKAKALLIO, Tiina, HÜSERS, Jens, PHIPPS, Laura, TIETZE, Mari F., VIEIRA-MARQUES, Pedro, and HÜBNER, Ursula H.

Abstract

Digitalization in healthcare and the increasing availability of data demand data literacy competences of nurses and other healthcare professionals including technical, ethical and communication skills. The international Spring School 2023 "Information in Healthcare - From Date to Knowledge" aimed at these competences covering interoperability, data protection and security, data analytics and ethical issues. These topics were embedded in the overall case of data-driven quality improvement for diabetes patients in a region. The curriculum includes an online preparation-phase and a five-days attendance week, incorporating problem-based and group work approaches. According to the student's evaluation, the awareness of the importance of the topics was raised and theoretical as well as practical application skills were improved. The Spring School enhanced data literacy competences, critical thinking, problem-solving, interprofessional und intercultural skills among healthcare professionals. Such course offering can contribute to meeting the increasing challenges of digitalization in healthcare. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Integrating Health Informatics into Pre-Registration Nursing Education: Insights from a Participatory Workshop.

Author

LOKMIC-TOMKINS, Zerina, RAGHUNATHAN, Kalpana, ALMOND, Helen, BOOTH, Richard G., MCBRIDE, Susan G., TIETZE, Mari F., HONEY, Michelle, PROCTER, Paula, PEDDLE, Monica, and MCKENNA, Lisa

Abstract

The implementation of health informatics in pre-registration health professional degrees faces persistent challenges, including curriculum overload, educator workforce capability gaps, and financial constraints. Despite these barriers, reports of successful implementation of health informatics in pre-registration nursing programs exist. A virtual workshop was held during the 15th International Nursing Informatics Conference in 2021 with the aim to explore successful implementation strategies for incorporating health informatics into the nursing curriculum to meet the accreditation standards. This paper reports recommendations from the workshop emphasising the importance of academic-clinical partnerships to develop innovative approaches to enhance the capacity of academic teams and access to contemporary point of care digital technologies that reflect applications of health informatics in interdisciplinary clinical settings. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Presence of Human Papillomavirus and Epstein–Barr Virus, but Absence of Merkel Cell Polyomavirus, in Head and Neck Cancer of Non-Smokers and Non-Drinkers

Author

Frans J. Mulder, Faisal Klufah, Famke M. E. Janssen, Farzaneh Farshadpour, Stefan M. Willems, Remco de Bree, Axel zur Hausen, Mari F. C. M. van den Hout, Bernd Kremer, and Ernst-Jan M. Speel

Subjects
head and neck cancer, human papillomavirus, Epstein–Barr virus, polyomavirus, non-smokers, non-drinkers, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

ObjectiveDetermine the presence and prognostic value of human papillomavirus (HPV), Epstein-Barr virus (EBV), Merkel cell polyomavirus (MCPyV), and cell cycle proteins in head and neck squamous cell carcinoma (HNSCC) of non-smokers and non-drinkers (NSND).MethodsClinical characteristics and tumors of 119 NSND with HNSCC were retrospectively collected and analyzed on tissue microarrays. RNAscope in situ hybridization (ISH) was used to screen for the presence of HPV and MCPyV mRNA. Immunohistochemistry was performed for expression of p16 as surrogate marker for HPV, Large T-antigen for MCPyV, and cell cycle proteins p53 and pRb. Positive virus results were confirmed with polymerase chain reaction. For EBV, EBV encoded RNA ISH was performed. Differences in 5-year survival between virus positive and negative tumors were determined by log rank analysis.ResultsAll oropharyngeal tumors (OPSCC) (n = 10) were HPV-positive, in addition to one oral (OSCC) and one nasopharyngeal tumor (NPSCC). The other three NPSCC were EBV-positive. MCPyV was not detected. Patients with HPV or EBV positive tumors did not have a significantly better 5-year disease free or overall survival. Over 70% of virus negative OSCC showed mutant-type p53 expression.ConclusionIn this cohort, all OPSCC and NPSCC showed HPV or EBV presence. Besides one OSCC, all other oral (n = 94), hypopharyngeal (n = 1), and laryngeal (n = 9) tumors were HPV, EBV, and MCPyV negative. This argues against a central role of these viruses in the ethiopathogenesis of tumors outside the oro- and nasopharynx in NSND. So, for the majority of NSND with virus negative OSCC, more research is needed to understand the carcinogenic mechanisms in order to consider targeted therapeutic options.

Published
2021
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35. In the mix: the potential benefits of adding GM-CSF to CpG-B in the local treatment of patients with early-stage melanoma

Author

Bas D. Koster, Tamarah D. de Jong, Mari F. C. M. van den Hout, Berbel J. R. Sluijter, Ronald J. C. L. M. Vuylsteke, Barbara G. Molenkamp, Saskia Vosslamber, M. Petrousjka van den Tol, Alfons J. M. van den Eertwegh, and Tanja D. de Gruijl

Subjects
gm-csf, cpg, melanoma, dendritic cells, sentinel lymph node, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Whereas TLR9 agonists are recognized as powerful stimulators of antitumor immunity, GM-CSF has had mixed reviews. In previously reported randomized trials we assessed the effects of local immune modulation in early-stage melanoma with CpG-B alone or with GM-CSF. Here we discuss the added value of GM-CSF and show sex-related differences.

Published
2020
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36. Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus–Positive Oropharyngeal Carcinoma

Author

Cavalieri, Stefano, Serafini, Mara S., Carenzo, Andrea, Canevari, Silvana, Brakenhoff, Ruud H., Leemans, C. René, Nauta, Irene H., Hoebers, Frank, van den Hout, Mari F. C. M., Scheckenbach, Kathrin, Hoffmann, Thomas K., Ardighieri, Laura, Poli, Tito, Quattrone, Pasquale, Locati, Laura D., Licitra, Lisa, and De Cecco, Loris

Published
2021
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37. Creating Case Studies for Digital Health and Technology Competency in Nursing.

Author

Kunkel, Dorcas E., Tietze, Mari F., Wilson, Marisa, Fant, Catherine T., Rivard, Mary Jane, Belchez, Chito A., Forman, Tracia M., and Husson, Nancy M.

Abstract

Background: Nursing programs and their faculty must ensure that graduates have the informatics, digital health, and health care technologies competencies needed by health systems. Problem: A gap exists in nursing faculty knowledge, skills, and abilities for incorporating informatics, digital health, and technologies across curricula because of low focus on this area in faculty development initiatives and rapid adoption and evolution of technologies in health care systems. Approach: The Nursing Knowledge Big Data Science initiative Education Subgroup used a process to create case studies for including informatics, digital health, and the concomitant clinical reasoning/critical thinking competencies across curricula. Outcomes: Three case study examples were created using the process. Conclusions: The process for creating case studies that incorporate required informatics, digital health, and health care technologies can be used by nursing educators for teaching across their curricula and to assess student competency. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Buoyancy forcing: a key driver of northern North Atlantic sea surface temperature variability across multiple timescales

Author

Risebrobakken, Bjørg, Jensen, Mari F., Langehaug, Helene R., Eldevik, Tor, Sandø, Anne Britt, Li, Camille, Born, Andreas, McClymont, Erin Louise, Salzmann, Ulrich, and Schepper, Stijn

Abstract

Analyses of observational data (from year 1870 AD) show that sea surface temperature (SST) anomalies along the pathway of Atlantic Water transport in the North Atlantic, the Norwegian Sea and the Iceland Sea are spatially coherent at multidecadal timescales. Spatially coherent SST anomalies are also observed over hundreds of thousands of years during parts of the Pliocene (5.23–5.03, 4.63–4.43, and 4.33–4.03 Ma). However, when investigating CMIP6 (Coupled Model Intercomparison Project 6) SSP126 (Shared Socioeconomic Pathway) future scenario runs (next century) and other Pliocene time intervals, the following three additional SST relations emerge: (1) the Norwegian Sea SST anomaly is dissimilar to the North Atlantic and the Iceland Sea SST anomalies (Pliocene; 4.93–4.73 and 3.93–3.63 Ma), (2) the Iceland Sea SST anomaly is dissimilar to the North Atlantic and the Norwegian Sea SST anomalies (Pliocene; 3.43–3.23 Ma), and (3) the North Atlantic SST anomaly is dissimilar to the SST anomalies of the Norwegian and Iceland seas (future trend). Hence, spatially non-coherent SST anomalies may occur in equilibrium climates (Pliocene), as well as in response to transient forcing (CMIP6 SSP126 low-emission future scenario). Since buoyancy is a key forcing for the inflow of Atlantic Water to the Norwegian Sea, we investigate the impacts of buoyancy forcing on spatial relations between SST anomalies seen in the North Atlantic and the Norwegian and Iceland seas. This is done by performing a range of idealized experiments using the Massachusetts Institute of Technology general circulation model (MITgcm). Through these idealized experiments we can reproduce three out of four of the documented SST anomaly relations: being spatially coherent under weak to intermediate freshwater forcing over the Nordic Seas, the Iceland Sea being dissimilar to the North Atlantic and the Norwegian Sea under weak atmospheric warming over the Nordic Seas, and the North Atlantic being dissimilar to the Norwegian and Iceland seas under strong atmospheric warming over the Nordic Seas. We suggest that the unexplained SST anomaly relation, when the Norwegian Sea is dissimilar to the North Atlantic and the Iceland Sea, may reflect a response to a weakened Norwegian Atlantic Current compensated for by a strong Irminger Current or an expanded East Greenland Current.

Published
2023

40. Whole-genome sequencing reveals host factors underlying critical COVID-19

Author

Kousathanas, A, Pairo-Castineira, E, Rawlik, K, Stuckey, A, Odhams, C, Walker, S, Russell, C, Malinauskas, T, Wu, Y, Millar, J, Shen, X, Elliott, K, Griffiths, F, Oosthuyzen, W, Morrice, K, Keating, S, Wang, B, Rhodes, D, Klaric, L, Zechner, M, Parkinson, N, Siddiq, A, Goddard, P, Donovan, S, Maslove, D, Nichol, A, Semple, M, Zainy, T, Maleady-Crowe, F, Todd, L, Salehi, S, Knight, J, Elgar, G, Chan, G, Arumugam, P, Patch, C, Rendon, A, Bentley, D, Kingsley, C, Kosmicki, J, Horowitz, J, Baras, A, Abecasis, G, Ferreira, M, Justice, A, Mirshahi, T, Oetjens, M, Rader, D, Ritchie, M, Verma, A, Fowler, T, Shankar-Hari, M, Summers, C, Hinds, C, Horby, P, Ling, L, Mcauley, D, Montgomery, H, Openshaw, P, Elliott, P, Walsh, T, Tenesa, A, Shelton, J, Shastri, A, Ye, C, Weldon, C, Filshtein-Sonmez, T, Coker, D, Symons, A, Esparza-Gordillo, J, Aslibekyan, S, Auton, A, Pathak, G, Karjalainen, J, Stevens, C, Andrews, S, Kanai, M, Cordioli, M, Polimanti, R, Pirinen, M, Harerimana, N, Veerapen, K, Wolford, B, Nguyen, H, Solomonson, M, Liao, R, Chwialkowska, K, Trankiem, A, Balaconis, M, Hayward, C, Richmond, A, Campbell, A, Morris, M, Fawns-Ritchie, C, Glessner, J, Shaw, D, Chang, X, Polikowski, H, Petty, L, Chen, H, Wanying, Z, Hakonarson, H, Porteous, D, Below, J, North, K, Mccormick, J, Timmers, P, Wilson, J, D'Mellow, K, Kerr, S, Niemi, M, Nkambul, L, von Hohenstaufen, K, Sobh, A, Eltoukhy, M, Yassen, A, Hegazy, M, Okasha, K, Eid, M, Moahmed, H, Shahin, D, El-Sherbiny, Y, Elhadidy, T, Abd Elghafar, M, El-Jawhari, J, Mohamed, A, Elnagdy, M, Samir, A, Abdel-Aziz, M, Khafaga, W, El-Lawaty, W, Torky, M, El-shanshory, M, Batini, C, Lee, P, Shrine, N, Williams, A, Tobin, M, Guyatt, A, John, C, Packer, R, Ali, A, Free, R, Wang, X, Wain, L, Hollox, E, Venn, L, Bee, C, Adams, E, Niavarani, A, Sharififard, B, Aliannejad, R, Amirsavadkouhi, A, Naderpour, Z, Tadi, H, Aleagha, A, Ahmadi, S, Moghaddam, S, Adamsara, A, Saeedi, M, Abdollahi, H, Hosseini, A, Chariyavilaskul, P, Chamnanphon, M, Suttichet, T, Shotelersuk, V, Pongpanich, M, Phokaew, C, Chetruengchai, W, Jantarabenjakul, W, Putchareon, O, Torvorapanit, P, Puthanakit, T, Suchartlikitwong, P, Hirankarn, N, Nilaratanakul, V, Sodsai, P, Brumpton, B, Hveem, K, Willer, C, Zhou, W, Rogne, T, Solligard, E, Asvold, B, Abedalthagafi, M, Alaamery, M, Alqahtani, S, Barakeh, D, Al Harthi, F, Alsolm, E, Safieh, L, Alowayn, A, Alqubaishi, F, Al Mutairi, A, Mangul, S, Alshareef, A, Sawaji, M, Almutairi, M, Aljawini, N, Albesher, N, Arabi, Y, Mahmoud, E, Khattab, A, Halawani, R, Alahmadey, Z, Albakri, J, Felemban, W, Suliman, B, Hasanato, R, Al-Awdah, L, Alghamdi, J, Alzahrani, D, Aljohani, S, Al-Afghani, H, Alrashed, M, Aldhawi, N, Albardis, H, Alkwai, S, Alswailm, M, Almalki, F, Albeladi, M, Almohammed, I, Barhoush, E, Albader, A, Massadeh, S, Almalik, A, Alotaibi, S, Alghamdi, B, Jung, J, Fawzy, M, Lee, Y, Magnus, P, Trogstad, L, Helgeland, O, Harris, J, Mangino, M, Spector, T, Duncan, E, Smieszek, S, Przychodzen, B, Polymeropoulos, C, Polymeropoulos, V, Polymeropoulos, M, Fernandez-Cadenas, I, Perez-Tur, J, Llucia-Carol, L, Cullell, N, Muino, E, Carcel-Marquez, J, Dediego, M, Iglesias, L, Planas, A, Soriano, A, Rico, V, Aguero, D, Bedini, J, Lozano, F, Domingo, C, Robles, V, Ruiz-Jaen, F, Marquez, L, Gomez, J, Coto, E, Albaiceta, G, Garcia-Clemente, M, Dalmau, D, Arranz, M, Dietl, B, Serra-Llovich, A, Soler, P, Colobran, R, Martin-Nalda, A, Martinez, A, Bernardo, D, Rojo, S, Fiz-Lopez, A, Arribas, E, de la Cal-Sabater, P, Segura, T, Gonzalez-Villa, E, Serrano-Heras, G, Marti-Fabregas, J, Jimenez-Xarrie, E, de Felipe Mimbrera, A, Masjuan, J, Garcia-Madrona, S, Dominguez-Mayoral, A, Villalonga, J, Menendez-Valladares, P, Chasman, D, Buring, J, Ridker, P, Franco, G, Sesso, H, Manson, J, Medina-Gomez, C, Uitterlinden, A, Ikram, M, Kristiansson, K, Koskelainen, S, Perola, M, Donner, K, Kivinen, K, Palotie, A, Ripatti, S, Ruotsalainen, S, Kaunisto, M, Nakanishi, T, Butler-Laporte, G, Forgetta, V, Morrison, D, Ghosh, B, Laurent, L, Belisle, A, Henry, D, Abdullah, T, Adeleye, O, Mamlouk, N, Kimchi, N, Afrasiabi, Z, Rezk, N, Vulesevic, B, Bouab, M, Guzman, C, Petitjean, L, Tselios, C, Xue, X, Schurr, E, Afilalo, J, Afilalo, M, Oliveira, M, Brenner, B, Lepage, P, Ragoussis, J, Auld, D, Brassard, N, Durand, M, Chasse, M, Kaufmann, D, Lathrop, G, Mooser, V, Richards, J, Li, R, Adra, D, Rahmouni, S, Georges, M, Moutschen, M, Misset, B, Darcis, G, Guiot, J, Guntz, J, Azarzar, S, Gofflot, S, Beguin, Y, Claassen, S, Malaise, O, Huynen, P, Meuris, C, Thys, M, Jacques, J, Leonard, P, Frippiat, F, Giot, J, Sauvage, A, von Frenckell, C, Belhaj, Y, Lambermont, B, Pigazzini, S, Nkambule, L, Daya, M, Shortt, J, Rafaels, N, Wicks, S, Crooks, K, Barnes, K, Gignoux, C, Chavan, S, Laisk, T, Lall, K, Lepamets, M, Magi, R, Esko, T, Reimann, E, Milani, L, Alavere, H, Metsalu, K, Puusepp, M, Metspalu, A, Naaber, P, Laane, E, Pesukova, J, Peterson, P, Kisand, K, Tabri, J, Allos, R, Hensen, K, Starkopf, J, Ringmets, I, Tamm, A, Kallaste, A, Bochud, P, Rivolta, C, Bibert, S, Quinodoz, M, Kamdar, D, Boillat, N, Nussle, S, Albrich, W, Suh, N, Neofytos, D, Erard, V, Voide, C, de Cid, R, Galvan-Femenia, I, Blay, N, Carreras, A, Cortes, B, Farre, X, Sumoy, L, Moreno, V, Mercader, J, Guindo-Martinez, M, Torrents, D, Kogevinas, M, Garcia-Aymerich, J, Castano-Vinyals, G, Dobano, C, Renieri, A, Mari, F, Fallerini, C, Daga, S, Benetti, E, Baldassarri, M, Fava, F, Frullanti, E, Valentino, F, Doddato, G, Giliberti, A, Tita, R, Amitrano, S, Bruttini, M, Croci, S, Meloni, I, Mencarelli, M, Rizzo, C, Pinto, A, Beligni, G, Tommasi, A, Di Sarno, L, Palmieri, M, Carriero, M, Alaverdian, D, Busani, S, Bruno, R, Vecchia, M, Belli, M, Picchiotti, N, Sanarico, M, Gori, M, Furini, S, Mantovani, S, Ludovisi, S, Mondelli, M, Castelli, F, Quiros-Roldan, E, Antoni, M, Zanella, I, Vaghi, M, Rusconi, S, Siano, M, Montagnani, F, Emiliozzi, A, Fabbiani, M, Rossetti, B, Bargagli, E, Bergantini, L, D'Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Bandini, M, Caldarelli, G, Piacentini, P, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Ognibene, A, Pancrazzi, A, Lorubbio, M, D'Arminio Monforte, A, Miraglia, F, Girardis, M, Venturelli, S, Cossarizza, A, Antinori, A, Vergori, A, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Scotton, P, Andretta, F, Panese, S, Scaggiante, R, Gatti, F, Parisi, S, Baratti, S, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Merla, G, Squeo, G, Aucella, F, Raggi, P, Marciano, C, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Valente, S, Mandala, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Coviello, D, Mussini, C, Martinelli, E, Mancarella, S, Tavecchia, L, Crotti, L, Gabbi, C, Rizzi, M, Maggiolo, F, Ripamonti, D, Bachetti, T, La Rovere, M, Sarzi-Braga, S, Bussotti, M, Ceri, S, Pinoli, P, Raimondi, F, Biscarini, F, Stella, A, Zguro, K, Capitani, K, Suardi, C, Dei, S, Parati, G, Ravaglia, S, Artuso, R, Botta, G, Di Domenico, P, Rancan, I, Perrella, A, Bianchi, F, Romani, D, Bergomi, P, Catena, E, Colombo, R, Tanfoni, M, Vincenti, A, Ferri, C, Grassi, D, Pessina, G, Tumbarello, M, Di Pietro, M, Sabrina, R, Luchi, S, Barbieri, C, Acquilini, D, Andreucci, E, Segala, F, Tiseo, G, Falcone, M, Lista, M, Poscente, M, De Vivo, O, Petrocelli, P, Guarnaccia, A, Baroni, S, Smith, A, Boughton, A, Li, K, Lefaive, J, Annis, A, Chittoor, G, Josyula, N, Leader, J, Carey, D, Gass, M, Cantor, M, Yadav, A, van Heel, D, Hunt, K, Mason, D, Huang, Q, Finer, S, Trivedi, B, Griffiths, C, Martin, H, Wright, J, Trembath, R, Soranzo, N, Zhao, J, Butterworth, A, Danesh, J, Di Angelantonio, E, Franke, L, Boezen, M, Deelen, P, Claringbould, A, Lopera, E, Warmerdam, R, Vonk, J, van Blokland, I, Lanting, P, Ori, A, Zollner, S, Wang, J, Beck, A, Peloso, G, Ho, Y, Sun, Y, Huffman, J, O'Donnell, C, Cho, K, Tsao, P, Gaziano, J, Nivard, M, de Geus, E, Bartels, M, Jan Hottenga, J, Weiss, S, Karlson, E, Smoller, J, Green, R, Feng, Y, Murphy, S, Meigs, J, Woolley, A, Perez, E, Li, B, Verma, S, Lucas, A, Bradford, Y, Zeberg, H, Frithiof, R, Hultstrom, M, Lipcsey, M, Tardif, N, Rooyackers, O, Grip, J, Maricic, T, Karczewski, K, Atkinson, E, Tsuo, K, Baya, N, Turley, P, Gupta, R, Callier, S, Walters, R, Palmer, D, Sarma, G, Cheng, N, Lu, W, Bryant, S, Churchhouse, C, Cusick, C, Goldstein, J, King, D, Seed, C, Finucane, H, Martin, A, Satterstrom, F, Wilson, D, Armstrong, J, Rudkin, J, Band, G, Earle, S, Lin, S, Arning, N, Crook, D, Wyllie, D, O'Connell, A, Spencer, C, Koelling, N, Caulfield, M, Scott, R, Moutsianas, L, Pasko, D, Ball, C, Hong, E, Rand, K, Girshick, A, Guturu, H, Baltzell, A, Roberts, G, Park, D, Coignet, M, Mccurdy, S, Knight, S, Partha, R, Rhead, B, Zhang, M, Berkowitz, N, Gaddis, M, Noto, K, Ruiz, L, Pavlovic, M, Sloofman, L, Charney, A, Beckmann, N, Schadt, E, Jordan, D, Thompson, R, Gettler, K, Abul-Husn, N, Ascolillo, S, Buxbaum, J, Chaudhary, K, Cho, J, Itan, Y, Kenny, E, Belbin, G, Sealfon, S, Sebra, R, Salib, I, Collins, B, Levy, T, Britvan, B, Keller, K, Tang, L, Peruggia, M, Hiester, L, Niblo, K, Aksentijevich, A, Labkowsky, A, Karp, A, Zlatopolsky, M, Preuss, M, Loos, R, Nadkarni, G, Do, R, Hoggart, C, Choi, S, Underwood, S, O'Reilly, P, Huckins, L, Zyndorf, M, Daly, M, Neale, B, Ganna, A, Fawkes, A, Murphy, L, Rowan, K, Ponting, C, Vitart, V, Yang, J, Bretherick, A, Hendry, S, Law, A, Baillie, J, Kousathanas A., Pairo-Castineira E., Rawlik K., Stuckey A., Odhams C. A., Walker S., Russell C. D., Malinauskas T., Wu Y., Millar J., Shen X., Elliott K. S., Griffiths F., Oosthuyzen W., Morrice K., Keating S., Wang B., Rhodes D., Klaric L., Zechner M., Parkinson N., Siddiq A., Goddard P., Donovan S., Maslove D., Nichol A., Semple M. G., Zainy T., Maleady-Crowe F., Todd L., Salehi S., Knight J., Elgar G., Chan G., Arumugam P., Patch C., Rendon A., Bentley D., Kingsley C., Kosmicki J. A., Horowitz J. E., Baras A., Abecasis G. R., Ferreira M. A. R., Justice A., Mirshahi T., Oetjens M., Rader D. J., Ritchie M. D., Verma A., Fowler T. A., Shankar-Hari M., Summers C., Hinds C., Horby P., Ling L., McAuley D., Montgomery H., Openshaw P. J. M., Elliott P., Walsh T., Tenesa A., Shelton J. F., Shastri A. J., Ye C., Weldon C. H., Filshtein-Sonmez T., Coker D., Symons A., Esparza-Gordillo J., Aslibekyan S., Auton A., Pathak G. A., Karjalainen J., Stevens C., Andrews S. J., Kanai M., Cordioli M., Polimanti R., Pirinen M., Harerimana N., Veerapen K., Wolford B., Nguyen H., Solomonson M., Liao R. G., Chwialkowska K., Trankiem A., Balaconis M. K., Hayward C., Richmond A., Campbell A., Morris M., Fawns-Ritchie C., Glessner J. T., Shaw D. M., Chang X., Polikowski H., Petty L. E., Chen H. -H., Wanying Z., Hakonarson H., Porteous D. J., Below J., North K., McCormick J. B., Timmers P. R. H. J., Wilson J. F., D'Mellow K., Kerr S. M., Niemi M. E. K., Nkambul L., von Hohenstaufen K. A., Sobh A., Eltoukhy M. M., Yassen A. M., Hegazy M. A. F., Okasha K., Eid M. A., Moahmed H. S., Shahin D., El-Sherbiny Y. M., Elhadidy T. A., Abd Elghafar M. S., El-Jawhari J. J., Mohamed A. A. S., Elnagdy M. H., Samir A., Abdel-Aziz M., Khafaga W. T., El-Lawaty W. M., Torky M. S., El-shanshory M. R., Batini C., Lee P. H., Shrine N., Williams A. T., Tobin M. D., Guyatt A. L., John C., Packer R. J., Ali A., Free R. C., Wang X., Wain L. V., Hollox E. J., Venn L. D., Bee C. E., Adams E. L., Niavarani A., Sharififard B., Aliannejad R., Amirsavadkouhi A., Naderpour Z., Tadi H. A., Aleagha A. E., Ahmadi S., Moghaddam S. B. M., Adamsara A., Saeedi M., Abdollahi H., Hosseini A., Chariyavilaskul P., Chamnanphon M., Suttichet T. B., Shotelersuk V., Pongpanich M., Phokaew C., Chetruengchai W., Jantarabenjakul W., Putchareon O., Torvorapanit P., Puthanakit T., Suchartlikitwong P., Hirankarn N., Nilaratanakul V., Sodsai P., Brumpton B. M., Hveem K., Willer C., Zhou W., Rogne T., Solligard E., Asvold B. O., Abedalthagafi M., Alaamery M., Alqahtani S., Barakeh D., Al Harthi F., Alsolm E., Safieh L. A., Alowayn A. M., Alqubaishi F., Al Mutairi A., Mangul S., Alshareef A., Sawaji M., Almutairi M., Aljawini N., Albesher N., Arabi Y. M., Mahmoud E. S., Khattab A. K., Halawani R. T., Alahmadey Z. Z., Albakri J. K., Felemban W. A., Suliman B. A., Hasanato R., Al-Awdah L., Alghamdi J., AlZahrani D., AlJohani S., Al-Afghani H., Alrashed M., AlDhawi N., AlBardis H., Alkwai S., Alswailm M., Almalki F., Albeladi M., Almohammed I., Barhoush E., Albader A., Massadeh S., AlMalik A., Alotaibi S., Alghamdi B., Jung J., Fawzy M. S., Lee Y., Magnus P., Trogstad L. -I. S., Helgeland O., Harris J. R., Mangino M., Spector T. D., Duncan E., Smieszek S. P., Przychodzen B. P., Polymeropoulos C., Polymeropoulos V., Polymeropoulos M. H., Fernandez-Cadenas I., Perez-Tur J., Llucia-Carol L., Cullell N., Muino E., Carcel-Marquez J., DeDiego M. L., Iglesias L. L., Planas A. M., Soriano A., Rico V., Aguero D., Bedini J. L., Lozano F., Domingo C., Robles V., Ruiz-Jaen F., Marquez L., Gomez J., Coto E., Albaiceta G. M., Garcia-Clemente M., Dalmau D., Arranz M. J., Dietl B., Serra-Llovich A., Soler P., Colobran R., Martin-Nalda A., Martinez A. P., Bernardo D., Rojo S., Fiz-Lopez A., Arribas E., de la Cal-Sabater P., Segura T., Gonzalez-Villa E., Serrano-Heras G., Marti-Fabregas J., Jimenez-Xarrie E., de Felipe Mimbrera A., Masjuan J., Garcia-Madrona S., Dominguez-Mayoral A., Villalonga J. M., Menendez-Valladares P., Chasman D. I., Buring J. E., Ridker P. M., Franco G., Sesso H. D., Manson J. A. E., Glessner J. R., Medina-Gomez C., Uitterlinden A. G., Ikram M. A., Kristiansson K., Koskelainen S., Perola M., Donner K., Kivinen K., Palotie A., Ripatti S., Ruotsalainen S., Kaunisto M., Nakanishi T., Butler-Laporte G., Forgetta V., Morrison D. R., Ghosh B., Laurent L., Belisle A., Henry D., Abdullah T., Adeleye O., Mamlouk N., Kimchi N., Afrasiabi Z., Rezk N., Vulesevic B., Bouab M., Guzman C., Petitjean L., Tselios C., Xue X., Schurr E., Afilalo J., Afilalo M., Oliveira M., Brenner B., Lepage P., Ragoussis J., Auld D., Brassard N., Durand M., Chasse M., Kaufmann D. E., Lathrop G. M., Mooser V., Richards J. B., Li R., Adra D., Rahmouni S., Georges M., Moutschen M., Misset B., Darcis G., Guiot J., Guntz J., Azarzar S., Gofflot S., Beguin Y., Claassen S., Malaise O., Huynen P., Meuris C., Thys M., Jacques J., Leonard P., Frippiat F., Giot J. -B., Sauvage A. -S., von Frenckell C., Belhaj Y., Lambermont B., Pigazzini S., Nkambule L., Daya M., Shortt J., Rafaels N., Wicks S. J., Crooks K., Barnes K. C., Gignoux C. R., Chavan S., Laisk T., Lall K., Lepamets M., Magi R., Esko T., Reimann E., Milani L., Alavere H., Metsalu K., Puusepp M., Metspalu A., Naaber P., Laane E., Pesukova J., Peterson P., Kisand K., Tabri J., Allos R., Hensen K., Starkopf J., Ringmets I., Tamm A., Kallaste A., Bochud P. -Y., Rivolta C., Bibert S., Quinodoz M., Kamdar D., Boillat N., Nussle S. G., Albrich W., Suh N., Neofytos D., Erard V., Voide C., de Cid R., Galvan-Femenia I., Blay N., Carreras A., Cortes B., Farre X., Sumoy L., Moreno V., Mercader J. M., Guindo-Martinez M., Torrents D., Kogevinas M., Garcia-Aymerich J., Castano-Vinyals G., Dobano C., Renieri A., Mari F., Fallerini C., Daga S., Benetti E., Baldassarri M., Fava F., Frullanti E., Valentino F., Doddato G., Giliberti A., Tita R., Amitrano S., Bruttini M., Croci S., Meloni I., Mencarelli M. A., Rizzo C. L., Pinto A. M., Beligni G., Tommasi A., Di Sarno L., Palmieri M., Carriero M. L., Alaverdian D., Busani S., Bruno R., Vecchia M., Belli M. A., Picchiotti N., Sanarico M., Gori M., Furini S., Mantovani S., Ludovisi S., Mondelli M. U., Castelli F., Quiros-Roldan E., Antoni M. D., Zanella I., Vaghi M., Rusconi S., Siano M., Montagnani F., Emiliozzi A., Fabbiani M., Rossetti B., Bargagli E., Bergantini L., D'Alessandro M., Cameli P., Bennett D., Anedda F., Marcantonio S., Scolletta S., Franchi F., Mazzei M. A., Guerrini S., Conticini E., Cantarini L., Frediani B., Tacconi D., Spertilli C., Feri M., Donati A., Scala R., Guidelli L., Spargi G., Corridi M., Nencioni C., Croci L., Bandini M., Caldarelli G. P., Piacentini P., Desanctis E., Cappelli S., Canaccini A., Verzuri A., Anemoli V., Ognibene A., Pancrazzi A., Lorubbio M., D'Arminio Monforte A., Miraglia F. G., Girardis M., Venturelli S., Cossarizza A., Antinori A., Vergori A., Gabrieli A., Riva A., Francisci D., Schiaroli E., Paciosi F., Scotton P. G., Andretta F., Panese S., Scaggiante R., Gatti F., Parisi S. G., Baratti S., Della Monica M., Piscopo C., Capasso M., Russo R., Andolfo I., Iolascon A., Fiorentino G., Carella M., Castori M., Merla G., Squeo G. M., Aucella F., Raggi P., Marciano C., Perna R., Bassetti M., Di Biagio A., Sanguinetti M., Masucci L., Valente S., Mandala M., Giorli A., Salerni L., Zucchi P., Parravicini P., Menatti E., Trotta T., Giannattasio F., Coiro G., Lena F., Coviello D. A., Mussini C., Martinelli E., Mancarella S., Tavecchia L., Crotti L., Gabbi C., Rizzi M., Maggiolo F., Ripamonti D., Bachetti T., La Rovere M. T., Sarzi-Braga S., Bussotti M., Ceri S., Pinoli P., Raimondi F., Biscarini F., Stella A., Zguro K., Capitani K., Suardi C., Dei S., Parati G., Ravaglia S., Artuso R., Botta G., Di Domenico P., Rancan I., Perrella A., Bianchi F., Romani D., Bergomi P., Catena E., Colombo R., Tanfoni M., Vincenti A., Ferri C., Grassi D., Pessina G., Tumbarello M., Di Pietro M., Sabrina R., Luchi S., Barbieri C., Acquilini D., Andreucci E., Segala F. V., Tiseo G., Falcone M., Lista M., Poscente M., De Vivo O., Petrocelli P., Guarnaccia A., Baroni S., Smith A. V., Boughton A. P., Li K. W., LeFaive J., Annis A., Justice A. E., Chittoor G., Josyula N. S., Leader J. B., Carey D. J., Gass M. C., Cantor M. N., Yadav A., van Heel D. A., Hunt K. A., Mason D., Huang Q. Q., Finer S., Trivedi B., Griffiths C. J., Martin H. C., Wright J., Trembath R. C., Soranzo N., Zhao J. H., Butterworth A. S., Danesh J., Di Angelantonio E., Franke L., Boezen M., Deelen P., Claringbould A., Lopera E., Warmerdam R., Vonk J. M., van Blokland I., Lanting P., Ori A. P. S., Zollner S., Wang J., Beck A., Peloso G., Ho Y. -L., Sun Y. V., Huffman J. E., O'Donnell C. J., Cho K., Tsao P., Gaziano J. M., Nivard M., de Geus E., Bartels M., Jan Hottenga J., Weiss S. T., Karlson E. W., Smoller J. W., Green R. C., Feng Y. -C. A., Mercader J., Murphy S. N., Meigs J. B., Woolley A. E., Perez E. F., Rader D., Li B., Verma S. S., Lucas A., Bradford Y., Zeberg H., Frithiof R., Hultstrom M., Lipcsey M., Tardif N., Rooyackers O., Grip J., Maricic T., Karczewski K. J., Atkinson E. G., Tsuo K., Baya N., Turley P., Gupta R., Callier S., Walters R. K., Palmer D. S., Sarma G., Cheng N., Lu W., Bryant S., Churchhouse C., Cusick C., Goldstein J. I., King D., Seed C., Finucane H., Martin A. R., Satterstrom F. K., Wilson D. J., Armstrong J., Rudkin J. K., Band G., Earle S. G., Lin S. -K., Arning N., Crook D. W., Wyllie D. H., O'Connell A. M., Spencer C. C. A., Koelling N., Caulfield M. J., Scott R. H., Fowler T., Moutsianas L., Pasko D., Ball C. A., Hong E. L., Rand K., Girshick A., Guturu H., Baltzell A. H., Roberts G., Park D., Coignet M., McCurdy S., Knight S., Partha R., Rhead B., Zhang M., Berkowitz N., Gaddis M., Noto K., Ruiz L., Pavlovic M., Sloofman L. G., Charney A. W., Beckmann N. D., Schadt E. E., Jordan D. M., Thompson R. C., Gettler K., Abul-Husn N. S., Ascolillo S., Buxbaum J. D., Chaudhary K., Cho J. H., Itan Y., Kenny E. E., Belbin G. M., Sealfon S. C., Sebra R. P., Salib I., Collins B. L., Levy T., Britvan B., Keller K., Tang L., Peruggia M., Hiester L. L., Niblo K., Aksentijevich A., Labkowsky A., Karp A., Zlatopolsky M., Preuss M., Loos R. J. F., Nadkarni G. N., Do R., Hoggart C., Choi S., Underwood S. J., O'Reilly P., Huckins L. M., Zyndorf M., Daly M. J., Neale B. M., Ganna A., Fawkes A., Murphy L., Rowan K., Ponting C. P., Vitart V., Yang J., Bretherick A. D., Hendry S. C., Law A., Baillie J. K., Kousathanas, A, Pairo-Castineira, E, Rawlik, K, Stuckey, A, Odhams, C, Walker, S, Russell, C, Malinauskas, T, Wu, Y, Millar, J, Shen, X, Elliott, K, Griffiths, F, Oosthuyzen, W, Morrice, K, Keating, S, Wang, B, Rhodes, D, Klaric, L, Zechner, M, Parkinson, N, Siddiq, A, Goddard, P, Donovan, S, Maslove, D, Nichol, A, Semple, M, Zainy, T, Maleady-Crowe, F, Todd, L, Salehi, S, Knight, J, Elgar, G, Chan, G, Arumugam, P, Patch, C, Rendon, A, Bentley, D, Kingsley, C, Kosmicki, J, Horowitz, J, Baras, A, Abecasis, G, Ferreira, M, Justice, A, Mirshahi, T, Oetjens, M, Rader, D, Ritchie, M, Verma, A, Fowler, T, Shankar-Hari, M, Summers, C, Hinds, C, Horby, P, Ling, L, Mcauley, D, Montgomery, H, Openshaw, P, Elliott, P, Walsh, T, Tenesa, A, Shelton, J, Shastri, A, Ye, C, Weldon, C, Filshtein-Sonmez, T, Coker, D, Symons, A, Esparza-Gordillo, J, Aslibekyan, S, Auton, A, Pathak, G, Karjalainen, J, Stevens, C, Andrews, S, Kanai, M, Cordioli, M, Polimanti, R, Pirinen, M, Harerimana, N, Veerapen, K, Wolford, B, Nguyen, H, Solomonson, M, Liao, R, Chwialkowska, K, Trankiem, A, Balaconis, M, Hayward, C, Richmond, A, Campbell, A, Morris, M, Fawns-Ritchie, C, Glessner, J, Shaw, D, Chang, X, Polikowski, H, Petty, L, Chen, H, Wanying, Z, Hakonarson, H, Porteous, D, Below, J, North, K, Mccormick, J, Timmers, P, Wilson, J, D'Mellow, K, Kerr, S, Niemi, M, Nkambul, L, von Hohenstaufen, K, Sobh, A, Eltoukhy, M, Yassen, A, Hegazy, M, Okasha, K, Eid, M, Moahmed, H, Shahin, D, El-Sherbiny, Y, Elhadidy, T, Abd Elghafar, M, El-Jawhari, J, Mohamed, A, Elnagdy, M, Samir, A, Abdel-Aziz, M, Khafaga, W, El-Lawaty, W, Torky, M, El-shanshory, M, Batini, C, Lee, P, Shrine, N, Williams, A, Tobin, M, Guyatt, A, John, C, Packer, R, Ali, A, Free, R, Wang, X, Wain, L, Hollox, E, Venn, L, Bee, C, Adams, E, Niavarani, A, Sharififard, B, Aliannejad, R, Amirsavadkouhi, A, Naderpour, Z, Tadi, H, Aleagha, A, Ahmadi, S, Moghaddam, S, Adamsara, A, Saeedi, M, Abdollahi, H, Hosseini, A, Chariyavilaskul, P, Chamnanphon, M, Suttichet, T, Shotelersuk, V, Pongpanich, M, Phokaew, C, Chetruengchai, W, Jantarabenjakul, W, Putchareon, O, Torvorapanit, P, Puthanakit, T, Suchartlikitwong, P, Hirankarn, N, Nilaratanakul, V, Sodsai, P, Brumpton, B, Hveem, K, Willer, C, Zhou, W, Rogne, T, Solligard, E, Asvold, B, Abedalthagafi, M, Alaamery, M, Alqahtani, S, Barakeh, D, Al Harthi, F, Alsolm, E, Safieh, L, Alowayn, A, Alqubaishi, F, Al Mutairi, A, Mangul, S, Alshareef, A, Sawaji, M, Almutairi, M, Aljawini, N, Albesher, N, Arabi, Y, Mahmoud, E, Khattab, A, Halawani, R, Alahmadey, Z, Albakri, J, Felemban, W, Suliman, B, Hasanato, R, Al-Awdah, L, Alghamdi, J, Alzahrani, D, Aljohani, S, Al-Afghani, H, Alrashed, M, Aldhawi, N, Albardis, H, Alkwai, S, Alswailm, M, Almalki, F, Albeladi, M, Almohammed, I, Barhoush, E, Albader, A, Massadeh, S, Almalik, A, Alotaibi, S, Alghamdi, B, Jung, J, Fawzy, M, Lee, Y, Magnus, P, Trogstad, L, Helgeland, O, Harris, J, Mangino, M, Spector, T, Duncan, E, Smieszek, S, Przychodzen, B, Polymeropoulos, C, Polymeropoulos, V, Polymeropoulos, M, Fernandez-Cadenas, I, Perez-Tur, J, Llucia-Carol, L, Cullell, N, Muino, E, Carcel-Marquez, J, Dediego, M, Iglesias, L, Planas, A, Soriano, A, Rico, V, Aguero, D, Bedini, J, Lozano, F, Domingo, C, Robles, V, Ruiz-Jaen, F, Marquez, L, Gomez, J, Coto, E, Albaiceta, G, Garcia-Clemente, M, Dalmau, D, Arranz, M, Dietl, B, Serra-Llovich, A, Soler, P, Colobran, R, Martin-Nalda, A, Martinez, A, Bernardo, D, Rojo, S, Fiz-Lopez, A, Arribas, E, de la Cal-Sabater, P, Segura, T, Gonzalez-Villa, E, Serrano-Heras, G, Marti-Fabregas, J, Jimenez-Xarrie, E, de Felipe Mimbrera, A, Masjuan, J, Garcia-Madrona, S, Dominguez-Mayoral, A, Villalonga, J, Menendez-Valladares, P, Chasman, D, Buring, J, Ridker, P, Franco, G, Sesso, H, Manson, J, Medina-Gomez, C, Uitterlinden, A, Ikram, M, Kristiansson, K, Koskelainen, S, Perola, M, Donner, K, Kivinen, K, Palotie, A, Ripatti, S, Ruotsalainen, S, Kaunisto, M, Nakanishi, T, Butler-Laporte, G, Forgetta, V, Morrison, D, Ghosh, B, Laurent, L, Belisle, A, Henry, D, Abdullah, T, Adeleye, O, Mamlouk, N, Kimchi, N, Afrasiabi, Z, Rezk, N, Vulesevic, B, Bouab, M, Guzman, C, Petitjean, L, Tselios, C, Xue, X, Schurr, E, Afilalo, J, Afilalo, M, Oliveira, M, Brenner, B, Lepage, P, Ragoussis, J, Auld, D, Brassard, N, Durand, M, Chasse, M, Kaufmann, D, Lathrop, G, Mooser, V, Richards, J, Li, R, Adra, D, Rahmouni, S, Georges, M, Moutschen, M, Misset, B, Darcis, G, Guiot, J, Guntz, J, Azarzar, S, Gofflot, S, Beguin, Y, Claassen, S, Malaise, O, Huynen, P, Meuris, C, Thys, M, Jacques, J, Leonard, P, Frippiat, F, Giot, J, Sauvage, A, von Frenckell, C, Belhaj, Y, Lambermont, B, Pigazzini, S, Nkambule, L, Daya, M, Shortt, J, Rafaels, N, Wicks, S, Crooks, K, Barnes, K, Gignoux, C, Chavan, S, Laisk, T, Lall, K, Lepamets, M, Magi, R, Esko, T, Reimann, E, Milani, L, Alavere, H, Metsalu, K, Puusepp, M, Metspalu, A, Naaber, P, Laane, E, Pesukova, J, Peterson, P, Kisand, K, Tabri, J, Allos, R, Hensen, K, Starkopf, J, Ringmets, I, Tamm, A, Kallaste, A, Bochud, P, Rivolta, C, Bibert, S, Quinodoz, M, Kamdar, D, Boillat, N, Nussle, S, Albrich, W, Suh, N, Neofytos, D, Erard, V, Voide, C, de Cid, R, Galvan-Femenia, I, Blay, N, Carreras, A, Cortes, B, Farre, X, Sumoy, L, Moreno, V, Mercader, J, Guindo-Martinez, M, Torrents, D, Kogevinas, M, Garcia-Aymerich, J, Castano-Vinyals, G, Dobano, C, Renieri, A, Mari, F, Fallerini, C, Daga, S, Benetti, E, Baldassarri, M, Fava, F, Frullanti, E, Valentino, F, Doddato, G, Giliberti, A, Tita, R, Amitrano, S, Bruttini, M, Croci, S, Meloni, I, Mencarelli, M, Rizzo, C, Pinto, A, Beligni, G, Tommasi, A, Di Sarno, L, Palmieri, M, Carriero, M, Alaverdian, D, Busani, S, Bruno, R, Vecchia, M, Belli, M, Picchiotti, N, Sanarico, M, Gori, M, Furini, S, Mantovani, S, Ludovisi, S, Mondelli, M, Castelli, F, Quiros-Roldan, E, Antoni, M, Zanella, I, Vaghi, M, Rusconi, S, Siano, M, Montagnani, F, Emiliozzi, A, Fabbiani, M, Rossetti, B, Bargagli, E, Bergantini, L, D'Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Bandini, M, Caldarelli, G, Piacentini, P, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Ognibene, A, Pancrazzi, A, Lorubbio, M, D'Arminio Monforte, A, Miraglia, F, Girardis, M, Venturelli, S, Cossarizza, A, Antinori, A, Vergori, A, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Scotton, P, Andretta, F, Panese, S, Scaggiante, R, Gatti, F, Parisi, S, Baratti, S, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Merla, G, Squeo, G, Aucella, F, Raggi, P, Marciano, C, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Valente, S, Mandala, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Coviello, D, Mussini, C, Martinelli, E, Mancarella, S, Tavecchia, L, Crotti, L, Gabbi, C, Rizzi, M, Maggiolo, F, Ripamonti, D, Bachetti, T, La Rovere, M, Sarzi-Braga, S, Bussotti, M, Ceri, S, Pinoli, P, Raimondi, F, Biscarini, F, Stella, A, Zguro, K, Capitani, K, Suardi, C, Dei, S, Parati, G, Ravaglia, S, Artuso, R, Botta, G, Di Domenico, P, Rancan, I, Perrella, A, Bianchi, F, Romani, D, Bergomi, P, Catena, E, Colombo, R, Tanfoni, M, Vincenti, A, Ferri, C, Grassi, D, Pessina, G, Tumbarello, M, Di Pietro, M, Sabrina, R, Luchi, S, Barbieri, C, Acquilini, D, Andreucci, E, Segala, F, Tiseo, G, Falcone, M, Lista, M, Poscente, M, De Vivo, O, Petrocelli, P, Guarnaccia, A, Baroni, S, Smith, A, Boughton, A, Li, K, Lefaive, J, Annis, A, Chittoor, G, Josyula, N, Leader, J, Carey, D, Gass, M, Cantor, M, Yadav, A, van Heel, D, Hunt, K, Mason, D, Huang, Q, Finer, S, Trivedi, B, Griffiths, C, Martin, H, Wright, J, Trembath, R, Soranzo, N, Zhao, J, Butterworth, A, Danesh, J, Di Angelantonio, E, Franke, L, Boezen, M, Deelen, P, Claringbould, A, Lopera, E, Warmerdam, R, Vonk, J, van Blokland, I, Lanting, P, Ori, A, Zollner, S, Wang, J, Beck, A, Peloso, G, Ho, Y, Sun, Y, Huffman, J, O'Donnell, C, Cho, K, Tsao, P, Gaziano, J, Nivard, M, de Geus, E, Bartels, M, Jan Hottenga, J, Weiss, S, Karlson, E, Smoller, J, Green, R, Feng, Y, Murphy, S, Meigs, J, Woolley, A, Perez, E, Li, B, Verma, S, Lucas, A, Bradford, Y, Zeberg, H, Frithiof, R, Hultstrom, M, Lipcsey, M, Tardif, N, Rooyackers, O, Grip, J, Maricic, T, Karczewski, K, Atkinson, E, Tsuo, K, Baya, N, Turley, P, Gupta, R, Callier, S, Walters, R, Palmer, D, Sarma, G, Cheng, N, Lu, W, Bryant, S, Churchhouse, C, Cusick, C, Goldstein, J, King, D, Seed, C, Finucane, H, Martin, A, Satterstrom, F, Wilson, D, Armstrong, J, Rudkin, J, Band, G, Earle, S, Lin, S, Arning, N, Crook, D, Wyllie, D, O'Connell, A, Spencer, C, Koelling, N, Caulfield, M, Scott, R, Moutsianas, L, Pasko, D, Ball, C, Hong, E, Rand, K, Girshick, A, Guturu, H, Baltzell, A, Roberts, G, Park, D, Coignet, M, Mccurdy, S, Knight, S, Partha, R, Rhead, B, Zhang, M, Berkowitz, N, Gaddis, M, Noto, K, Ruiz, L, Pavlovic, M, Sloofman, L, Charney, A, Beckmann, N, Schadt, E, Jordan, D, Thompson, R, Gettler, K, Abul-Husn, N, Ascolillo, S, Buxbaum, J, Chaudhary, K, Cho, J, Itan, Y, Kenny, E, Belbin, G, Sealfon, S, Sebra, R, Salib, I, Collins, B, Levy, T, Britvan, B, Keller, K, Tang, L, Peruggia, M, Hiester, L, Niblo, K, Aksentijevich, A, Labkowsky, A, Karp, A, Zlatopolsky, M, Preuss, M, Loos, R, Nadkarni, G, Do, R, Hoggart, C, Choi, S, Underwood, S, O'Reilly, P, Huckins, L, Zyndorf, M, Daly, M, Neale, B, Ganna, A, Fawkes, A, Murphy, L, Rowan, K, Ponting, C, Vitart, V, Yang, J, Bretherick, A, Hendry, S, Law, A, Baillie, J, Kousathanas A., Pairo-Castineira E., Rawlik K., Stuckey A., Odhams C. A., Walker S., Russell C. D., Malinauskas T., Wu Y., Millar J., Shen X., Elliott K. S., Griffiths F., Oosthuyzen W., Morrice K., Keating S., Wang B., Rhodes D., Klaric L., Zechner M., Parkinson N., Siddiq A., Goddard P., Donovan S., Maslove D., Nichol A., Semple M. G., Zainy T., Maleady-Crowe F., Todd L., Salehi S., Knight J., Elgar G., Chan G., Arumugam P., Patch C., Rendon A., Bentley D., Kingsley C., Kosmicki J. A., Horowitz J. E., Baras A., Abecasis G. R., Ferreira M. A. R., Justice A., Mirshahi T., Oetjens M., Rader D. J., Ritchie M. D., Verma A., Fowler T. A., Shankar-Hari M., Summers C., Hinds C., Horby P., Ling L., McAuley D., Montgomery H., Openshaw P. J. M., Elliott P., Walsh T., Tenesa A., Shelton J. F., Shastri A. J., Ye C., Weldon C. H., Filshtein-Sonmez T., Coker D., Symons A., Esparza-Gordillo J., Aslibekyan S., Auton A., Pathak G. A., Karjalainen J., Stevens C., Andrews S. J., Kanai M., Cordioli M., Polimanti R., Pirinen M., Harerimana N., Veerapen K., Wolford B., Nguyen H., Solomonson M., Liao R. G., Chwialkowska K., Trankiem A., Balaconis M. K., Hayward C., Richmond A., Campbell A., Morris M., Fawns-Ritchie C., Glessner J. T., Shaw D. M., Chang X., Polikowski H., Petty L. E., Chen H. -H., Wanying Z., Hakonarson H., Porteous D. J., Below J., North K., McCormick J. B., Timmers P. R. H. J., Wilson J. F., D'Mellow K., Kerr S. M., Niemi M. E. K., Nkambul L., von Hohenstaufen K. A., Sobh A., Eltoukhy M. M., Yassen A. M., Hegazy M. A. F., Okasha K., Eid M. A., Moahmed H. S., Shahin D., El-Sherbiny Y. M., Elhadidy T. A., Abd Elghafar M. S., El-Jawhari J. J., Mohamed A. A. S., Elnagdy M. H., Samir A., Abdel-Aziz M., Khafaga W. T., El-Lawaty W. M., Torky M. S., El-shanshory M. R., Batini C., Lee P. H., Shrine N., Williams A. T., Tobin M. D., Guyatt A. L., John C., Packer R. J., Ali A., Free R. C., Wang X., Wain L. V., Hollox E. J., Venn L. D., Bee C. E., Adams E. L., Niavarani A., Sharififard B., Aliannejad R., Amirsavadkouhi A., Naderpour Z., Tadi H. A., Aleagha A. E., Ahmadi S., Moghaddam S. B. M., Adamsara A., Saeedi M., Abdollahi H., Hosseini A., Chariyavilaskul P., Chamnanphon M., Suttichet T. B., Shotelersuk V., Pongpanich M., Phokaew C., Chetruengchai W., Jantarabenjakul W., Putchareon O., Torvorapanit P., Puthanakit T., Suchartlikitwong P., Hirankarn N., Nilaratanakul V., Sodsai P., Brumpton B. M., Hveem K., Willer C., Zhou W., Rogne T., Solligard E., Asvold B. O., Abedalthagafi M., Alaamery M., Alqahtani S., Barakeh D., Al Harthi F., Alsolm E., Safieh L. A., Alowayn A. M., Alqubaishi F., Al Mutairi A., Mangul S., Alshareef A., Sawaji M., Almutairi M., Aljawini N., Albesher N., Arabi Y. M., Mahmoud E. S., Khattab A. K., Halawani R. T., Alahmadey Z. Z., Albakri J. K., Felemban W. A., Suliman B. A., Hasanato R., Al-Awdah L., Alghamdi J., AlZahrani D., AlJohani S., Al-Afghani H., Alrashed M., AlDhawi N., AlBardis H., Alkwai S., Alswailm M., Almalki F., Albeladi M., Almohammed I., Barhoush E., Albader A., Massadeh S., AlMalik A., Alotaibi S., Alghamdi B., Jung J., Fawzy M. S., Lee Y., Magnus P., Trogstad L. -I. S., Helgeland O., Harris J. R., Mangino M., Spector T. D., Duncan E., Smieszek S. P., Przychodzen B. P., Polymeropoulos C., Polymeropoulos V., Polymeropoulos M. H., Fernandez-Cadenas I., Perez-Tur J., Llucia-Carol L., Cullell N., Muino E., Carcel-Marquez J., DeDiego M. L., Iglesias L. L., Planas A. M., Soriano A., Rico V., Aguero D., Bedini J. L., Lozano F., Domingo C., Robles V., Ruiz-Jaen F., Marquez L., Gomez J., Coto E., Albaiceta G. M., Garcia-Clemente M., Dalmau D., Arranz M. J., Dietl B., Serra-Llovich A., Soler P., Colobran R., Martin-Nalda A., Martinez A. P., Bernardo D., Rojo S., Fiz-Lopez A., Arribas E., de la Cal-Sabater P., Segura T., Gonzalez-Villa E., Serrano-Heras G., Marti-Fabregas J., Jimenez-Xarrie E., de Felipe Mimbrera A., Masjuan J., Garcia-Madrona S., Dominguez-Mayoral A., Villalonga J. M., Menendez-Valladares P., Chasman D. I., Buring J. E., Ridker P. M., Franco G., Sesso H. D., Manson J. A. E., Glessner J. R., Medina-Gomez C., Uitterlinden A. G., Ikram M. A., Kristiansson K., Koskelainen S., Perola M., Donner K., Kivinen K., Palotie A., Ripatti S., Ruotsalainen S., Kaunisto M., Nakanishi T., Butler-Laporte G., Forgetta V., Morrison D. R., Ghosh B., Laurent L., Belisle A., Henry D., Abdullah T., Adeleye O., Mamlouk N., Kimchi N., Afrasiabi Z., Rezk N., Vulesevic B., Bouab M., Guzman C., Petitjean L., Tselios C., Xue X., Schurr E., Afilalo J., Afilalo M., Oliveira M., Brenner B., Lepage P., Ragoussis J., Auld D., Brassard N., Durand M., Chasse M., Kaufmann D. E., Lathrop G. M., Mooser V., Richards J. B., Li R., Adra D., Rahmouni S., Georges M., Moutschen M., Misset B., Darcis G., Guiot J., Guntz J., Azarzar S., Gofflot S., Beguin Y., Claassen S., Malaise O., Huynen P., Meuris C., Thys M., Jacques J., Leonard P., Frippiat F., Giot J. -B., Sauvage A. -S., von Frenckell C., Belhaj Y., Lambermont B., Pigazzini S., Nkambule L., Daya M., Shortt J., Rafaels N., Wicks S. J., Crooks K., Barnes K. C., Gignoux C. R., Chavan S., Laisk T., Lall K., Lepamets M., Magi R., Esko T., Reimann E., Milani L., Alavere H., Metsalu K., Puusepp M., Metspalu A., Naaber P., Laane E., Pesukova J., Peterson P., Kisand K., Tabri J., Allos R., Hensen K., Starkopf J., Ringmets I., Tamm A., Kallaste A., Bochud P. -Y., Rivolta C., Bibert S., Quinodoz M., Kamdar D., Boillat N., Nussle S. G., Albrich W., Suh N., Neofytos D., Erard V., Voide C., de Cid R., Galvan-Femenia I., Blay N., Carreras A., Cortes B., Farre X., Sumoy L., Moreno V., Mercader J. M., Guindo-Martinez M., Torrents D., Kogevinas M., Garcia-Aymerich J., Castano-Vinyals G., Dobano C., Renieri A., Mari F., Fallerini C., Daga S., Benetti E., Baldassarri M., Fava F., Frullanti E., Valentino F., Doddato G., Giliberti A., Tita R., Amitrano S., Bruttini M., Croci S., Meloni I., Mencarelli M. A., Rizzo C. L., Pinto A. M., Beligni G., Tommasi A., Di Sarno L., Palmieri M., Carriero M. L., Alaverdian D., Busani S., Bruno R., Vecchia M., Belli M. A., Picchiotti N., Sanarico M., Gori M., Furini S., Mantovani S., Ludovisi S., Mondelli M. U., Castelli F., Quiros-Roldan E., Antoni M. D., Zanella I., Vaghi M., Rusconi S., Siano M., Montagnani F., Emiliozzi A., Fabbiani M., Rossetti B., Bargagli E., Bergantini L., D'Alessandro M., Cameli P., Bennett D., Anedda F., Marcantonio S., Scolletta S., Franchi F., Mazzei M. A., Guerrini S., Conticini E., Cantarini L., Frediani B., Tacconi D., Spertilli C., Feri M., Donati A., Scala R., Guidelli L., Spargi G., Corridi M., Nencioni C., Croci L., Bandini M., Caldarelli G. P., Piacentini P., Desanctis E., Cappelli S., Canaccini A., Verzuri A., Anemoli V., Ognibene A., Pancrazzi A., Lorubbio M., D'Arminio Monforte A., Miraglia F. G., Girardis M., Venturelli S., Cossarizza A., Antinori A., Vergori A., Gabrieli A., Riva A., Francisci D., Schiaroli E., Paciosi F., Scotton P. G., Andretta F., Panese S., Scaggiante R., Gatti F., Parisi S. G., Baratti S., Della Monica M., Piscopo C., Capasso M., Russo R., Andolfo I., Iolascon A., Fiorentino G., Carella M., Castori M., Merla G., Squeo G. M., Aucella F., Raggi P., Marciano C., Perna R., Bassetti M., Di Biagio A., Sanguinetti M., Masucci L., Valente S., Mandala M., Giorli A., Salerni L., Zucchi P., Parravicini P., Menatti E., Trotta T., Giannattasio F., Coiro G., Lena F., Coviello D. A., Mussini C., Martinelli E., Mancarella S., Tavecchia L., Crotti L., Gabbi C., Rizzi M., Maggiolo F., Ripamonti D., Bachetti T., La Rovere M. T., Sarzi-Braga S., Bussotti M., Ceri S., Pinoli P., Raimondi F., Biscarini F., Stella A., Zguro K., Capitani K., Suardi C., Dei S., Parati G., Ravaglia S., Artuso R., Botta G., Di Domenico P., Rancan I., Perrella A., Bianchi F., Romani D., Bergomi P., Catena E., Colombo R., Tanfoni M., Vincenti A., Ferri C., Grassi D., Pessina G., Tumbarello M., Di Pietro M., Sabrina R., Luchi S., Barbieri C., Acquilini D., Andreucci E., Segala F. V., Tiseo G., Falcone M., Lista M., Poscente M., De Vivo O., Petrocelli P., Guarnaccia A., Baroni S., Smith A. V., Boughton A. P., Li K. W., LeFaive J., Annis A., Justice A. E., Chittoor G., Josyula N. S., Leader J. B., Carey D. J., Gass M. C., Cantor M. N., Yadav A., van Heel D. A., Hunt K. A., Mason D., Huang Q. Q., Finer S., Trivedi B., Griffiths C. J., Martin H. C., Wright J., Trembath R. C., Soranzo N., Zhao J. H., Butterworth A. S., Danesh J., Di Angelantonio E., Franke L., Boezen M., Deelen P., Claringbould A., Lopera E., Warmerdam R., Vonk J. M., van Blokland I., Lanting P., Ori A. P. S., Zollner S., Wang J., Beck A., Peloso G., Ho Y. -L., Sun Y. V., Huffman J. E., O'Donnell C. J., Cho K., Tsao P., Gaziano J. M., Nivard M., de Geus E., Bartels M., Jan Hottenga J., Weiss S. T., Karlson E. W., Smoller J. W., Green R. C., Feng Y. -C. A., Mercader J., Murphy S. N., Meigs J. B., Woolley A. E., Perez E. F., Rader D., Li B., Verma S. S., Lucas A., Bradford Y., Zeberg H., Frithiof R., Hultstrom M., Lipcsey M., Tardif N., Rooyackers O., Grip J., Maricic T., Karczewski K. J., Atkinson E. G., Tsuo K., Baya N., Turley P., Gupta R., Callier S., Walters R. K., Palmer D. S., Sarma G., Cheng N., Lu W., Bryant S., Churchhouse C., Cusick C., Goldstein J. I., King D., Seed C., Finucane H., Martin A. R., Satterstrom F. K., Wilson D. J., Armstrong J., Rudkin J. K., Band G., Earle S. G., Lin S. -K., Arning N., Crook D. W., Wyllie D. H., O'Connell A. M., Spencer C. C. A., Koelling N., Caulfield M. J., Scott R. H., Fowler T., Moutsianas L., Pasko D., Ball C. A., Hong E. L., Rand K., Girshick A., Guturu H., Baltzell A. H., Roberts G., Park D., Coignet M., McCurdy S., Knight S., Partha R., Rhead B., Zhang M., Berkowitz N., Gaddis M., Noto K., Ruiz L., Pavlovic M., Sloofman L. G., Charney A. W., Beckmann N. D., Schadt E. E., Jordan D. M., Thompson R. C., Gettler K., Abul-Husn N. S., Ascolillo S., Buxbaum J. D., Chaudhary K., Cho J. H., Itan Y., Kenny E. E., Belbin G. M., Sealfon S. C., Sebra R. P., Salib I., Collins B. L., Levy T., Britvan B., Keller K., Tang L., Peruggia M., Hiester L. L., Niblo K., Aksentijevich A., Labkowsky A., Karp A., Zlatopolsky M., Preuss M., Loos R. J. F., Nadkarni G. N., Do R., Hoggart C., Choi S., Underwood S. J., O'Reilly P., Huckins L. M., Zyndorf M., Daly M. J., Neale B. M., Ganna A., Fawkes A., Murphy L., Rowan K., Ponting C. P., Vitart V., Yang J., Bretherick A. D., Hendry S. C., Law A., and Baillie J. K.

Abstract

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

Published
2022

41. A first update on mapping the human genetic architecture of COVID-19

Author

COVID-19 Host Genetics Initiative, Pathak, GA, Karjalainen, J, Stevens, C, Neale, BM, Daly, M, Ganna, A, Andrews, SJ, Kanai, M, Cordioli, M, Polimanti, R, Harerimana, N, Pirinen, M, Liao, RG, Chwialkowska, K, Trankiem, A, Balaconis, MK, Nguyen, H, Solomonson, M, Veerapen, K, Wolford, B, Roberts, G, Park, D, Ball, CA, Coignet, M, McCurdy, S, Knight, S, Partha, R, Rhead, B, Zhang, M, Berkowitz, N, Gaddis, M, Noto, K, Ruiz, L, Pavlovic, M, Hong, EL, Rand, K, Girshick, A, Guturu, H, Baltzell, AH, Niemi, MEK, Rahmouni, S, Guntz, J, Beguin, Y, Pigazzini, S, Nkambule, L, Georges, M, Moutschen, M, Misset, B, Darcis, G, Guiot, J, Azarzar, S, Gofflot, S, Claassen, S, Malaise, O, Huynen, P, Meuris, C, Thys, M, Jacques, J, Leonard, P, Frippiat, F, Giot, J-B, Sauvage, A-S, Frenckell, CV, Belhaj, Y, Lambermont, B, Nakanishi, T, Morrison, DR, Mooser, V, Richards, JB, Butler-Laporte, G, Forgetta, V, Li, R, Ghosh, B, Laurent, L, Belisle, A, Henry, D, Abdullah, T, Adeleye, O, Mamlouk, N, Kimchi, N, Afrasiabi, Z, Rezk, N, Vulesevic, B, Bouab, M, Guzman, C, Petitjean, L, Tselios, C, Xue, X, Afilalo, J, Afilalo, M, Oliveira, M, Brenner, B, Brassard, N, Durand, M, Schurr, E, Lepage, P, Ragoussis, J, Auld, D, Chassé, M, Kaufmann, DE, Lathrop, GM, Adra, D, Hayward, C, Glessner, JT, Shaw, DM, Campbell, A, Morris, M, Hakonarson, H, Porteous, DJ, Below, J, Richmond, A, Chang, X, Polikowski, H, Lauren, PE, Chen, H-H, Wanying, Z, Fawns-Ritchie, C, North, K, McCormick, JB, Glessner, JR, Gignoux, CR, Wicks, SJ, Crooks, K, Barnes, KC, Daya, M, Shortt, J, Rafaels, N, Chavan, S, Timmers, PRHJ, Wilson, JF, Tenesa, A, Kerr, SM, D’Mellow, K, Shahin, D, El-Sherbiny, YM, von Hohenstaufen, KA, Sobh, A, Eltoukhy, MM, Nkambul, L, Elhadidy, TA, Abd Elghafar, MS, El-Jawhari, JJ, Mohamed, AAS, Elnagdy, MH, Samir, A, Abdel-Aziz, M, Khafaga, WT, El-Lawaty, WM, Torky, MS, El-shanshory, MR, Yassen, AM, Hegazy, MAF, Okasha, K, Eid, MA, Moahmed, HS, Medina-Gomez, C, Ikram, MA, Uitterlinden, AG, Mägi, R, Milani, L, Metspalu, A, Laisk, T, Läll, K, Lepamets, M, Esko, T, Reimann, E, Naaber, P, Laane, E, Pesukova, J, Peterson, P, Kisand, K, Tabri, J, Allos, R, Hensen, K, Starkopf, J, Ringmets, I, Tamm, A, Kallaste, A, Alavere, H, Metsalu, K, Puusepp, M, Batini, C, Tobin, MD, Venn, LD, Lee, PH, Shrine, N, Williams, AT, Guyatt, AL, John, C, Packer, RJ, Ali, A, Free, RC, Wang, X, Wain, LV, Hollox, EJ, Bee, CE, Adams, EL, Palotie, A, Ripatti, S, Ruotsalainen, S, Kristiansson, K, Koskelainen, S, Perola, M, Donner, K, Kivinen, K, Kaunisto, M, Rivolta, C, Bochud, P-Y, Bibert, S, Boillat, N, Nussle, SG, Albrich, W, Quinodoz, M, Kamdar, D, Suh, N, Neofytos, D, Erard, V, Voide, C, Friolet, R, Vollenweider, P, Pagani, JL, Oddo, M, zu Bentrup, FM, Conen, A, Clerc, O, Marchetti, O, Guillet, A, Guyat-Jacques, C, Foucras, S, Rime, M, Chassot, J, Jaquet, M, Viollet, RM, Lannepoudenx, Y, Portopena, L, Bochud, PY, Desgranges, F, Filippidis, P, Guéry, B, Haefliger, D, Kampouri, EE, Manuel, O, Munting, A, Papadimitriou-Olivgeris, M, Regina, J, Rochat-Stettler, L, Suttels, V, Tadini, E, Tschopp, J, Van Singer, M, Viala, B, Boillat-Blanco, N, Brahier, T, Hügli, O, Meuwly, JY, Pantet, O, Gonseth Nussle, S, Bochud, M, D’Acremont, V, Estoppey Younes, S, Albrich, WC, Cerny, A, O’Mahony, L, von Mering, C, Frischknecht, M, Kleger, G-R., Filipovic, M, Kahlert, CR, Wozniak, H, Negro, TR, Pugin, J, Bouras, K, Knapp, C, Egger, T, Perret, A, Montillier, P, di Bartolomeo, C, Barda, B, de Cid, R, Carreras, A, Moreno, V, Kogevinas, M, Galván-Femenía, I, Blay, N, Farré, X, Sumoy, L, Cortés, B, Mercader, JM, Guindo-Martinez, M, Torrents, D, Garcia-Aymerich, J, Castaño-Vinyals, G, Dobaño, C, Gori, M, Renieri, A, Mari, F, Mondelli, MU, Castelli, F, Vaghi, M, Rusconi, S, Montagnani, F, Bargagli, E, Franchi, F, Mazzei, MA, Cantarini, L, Tacconi, D, Feri, M, Scala, R, Spargi, G, Nencioni, C, Bandini, M, Caldarelli, GP, Canaccini, A, Ognibene, A, D’Arminio Monforte, A, Girardis, M, Antinori, A, Francisci, D, Schiaroli, E, Scotton, PG, Panese, S, Scaggiante, R, Monica, MD, Capasso, M, Fiorentino, G, Castori, M, Aucella, F, Biagio, AD, Masucci, L, Valente, S, Mandalà, M, Zucchi, P, Giannattasio, F, Coviello, DA, Mussini, C, Tavecchia, L, Crotti, L, Rizzi, M, Rovere, MTL, Sarzi-Braga, S, Bussotti, M, Ravaglia, S, Artuso, R, Perrella, A, Romani, D, Bergomi, P, Catena, E, Vincenti, A, Ferri, C, Grassi, D, Pessina, G, Tumbarello, M, Pietro, MD, Sabrina, R, Luchi, S, Furini, S, Dei, S, Benetti, E, Picchiotti, N, Sanarico, M, Ceri, S, Pinoli, P, Raimondi, F, Biscarini, F, Stella, A, Zguro, K, Capitani, K, Tanfoni, M, Fallerini, C, Daga, S, Baldassarri, M, Fava, F, Frullanti, E, Valentino, F, Doddato, G, Giliberti, A, Tita, R, Amitrano, S, Bruttini, M, Croci, S, Meloni, I, Mencarelli, MA, Rizzo, CL, Pinto, AM, Beligni, G, Tommasi, A, Sarno, LD, Palmieri, M, Carriero, ML, Alaverdian, D, Busani, S, Bruno, R, Vecchia, M, Belli, MA, Mantovani, S, Ludovisi, S, Quiros-Roldan, E, Antoni, MD, Zanella, I, Siano, M, Emiliozzi, A, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Guerrini, S, Conticini, E, Frediani, B, Spertilli, C, Donati, A, Guidelli, L, Corridi, M, Croci, L, Piacentini, P, Desanctis, E, Cappelli, S, Verzuri, A, Anemoli, V, Pancrazzi, A, Lorubbio, M, Miraglia, FG, Venturelli, S, Cossarizza, A, Vergori, A, Gabrieli, A, Riva, A, Paciosi, F, Andretta, F, Gatti, F, Parisi, SG, Baratti, S, Piscopo, C, Russo, R, Andolfo, I, Iolascon, A, Carella, M, Merla, G, Squeo, GM, Raggi, P, Marciano, C, Perna, R, Bassetti, M, Sanguinetti, M, Giorli, A, Salerni, L, Parravicini, P, Menatti, E, Trotta, T, Coiro, G, Lena, F, Martinelli, E, Mancarella, S, Gabbi, C, Maggiolo, F, Ripamonti, D, Bachetti, T, Suardi, C, Parati, G, Bottà, G, Domenico, PD, Rancan, I, Bianchi, F, Colombo, R, Barbieri, C, Acquilini, D, Andreucci, E, Segala, FV, Tiseo, G, Falcone, M, Lista, M, Poscente, M, Vivo, OD, Petrocelli, P, Guarnaccia, A, Baroni, S, van Heel, DA, Hunt, KA, Trembath, RC, Huang, QQ, Martin, HC, Mason, D, Trivedi, B, Wright, J, Finer, S, Akhtar, S, Anwar, M, Arciero, E, Ashraf, S, Breen, G, Chung, R, Curtis, CJ, Chowdhury, M, Colligan, G, Deloukas, P, Durham, C, Griffiths, C, Hurles, M, Hussain, S, Islam, K, Khan, A, Lavery, C, Lee, SH, Lerner, R, MacArthur, D, MacLaughlin, B, Martin, H, Miah, S, Newman, B, Safa, N, Tahmasebi, F, Griffiths, CJ, Smith, AV, Boughton, AP, Li, KW, LeFaive, J, Annis, A, Niavarani, A, Aliannejad, R, Sharififard, B, Amirsavadkouhi, A, Naderpour, Z, Tadi, HA, Aleagha, AE, Ahmadi, S, Moghaddam, SBM, Adamsara, A, Saeedi, M, Abdollahi, H, Hosseini, A, Chariyavilaskul, P, Jantarabenjakul, W, Hirankarn, N, Chamnanphon, M, Suttichet, TB, Shotelersuk, V, Pongpanich, M, Phokaew, C, Chetruengchai, W, Putchareon, O, Torvorapanit, P, Puthanakit, T, Suchartlikitwong, P, Nilaratanakul, V, Sodsai, P, Brumpton, BM, Hveem, K, Willer, C, Zhou, W, Rogne, T, Solligard, E, Åsvold, BO, Franke, L, Boezen, M, Deelen, P, Claringbould, A, Lopera, E, Warmerdam, R, Vonk, JM, van Blokland, I, Lanting, P, Ori, APS, Feng, Y-CA, Mercader, J, Weiss, ST, Karlson, EW, Smoller, JW, Murphy, SN, Meigs, JB, Woolley, AE, Green, RC, Perez, EF, Zöllner, S, Wang, J, Beck, A, Sloofman, LG, Ascolillo, S, Sebra, RP, Collins, BL, Levy, T, Buxbaum, JD, Sealfon, SC, Jordan, DM, Thompson, RC, Gettler, K, Chaudhary, K, Belbin, GM, Preuss, M, Hoggart, C, Choi, S, Underwood, SJ, Salib, I, Britvan, B, Keller, K, Tang, L, Peruggia, M, Hiester, LL, Niblo, K, Aksentijevich, A, Labkowsky, A, Karp, A, Zlatopolsky, M, Zyndorf, M, Charney, AW, Beckmann, ND, Schadt, EE, Abul-Husn, NS, Cho, JH, Itan, Y, Kenny, EE, Loos, RJF, Nadkarni, GN, Do, R, O’Reilly, P, Huckins, LM, Ferreira, MAR, Abecasis, GR, Leader, JB, Cantor, MN, Justice, AE, Carey, DJ, Chittoor, G, Josyula, NS, Kosmicki, JA, Horowitz, JE, Baras, A, Gass, MC, Yadav, A, Mirshahi, T, Hottenga, JJ, Bartels, M, de geus, EEJC, Nivard, MMG, Verma, A, Ritchie, MD, Rader, D, Li, B, Verma, SS, Lucas, A, Bradford, Y, Abedalthagafi, M, Alaamery, M, Alshareef, A, Sawaji, M, Massadeh, S, AlMalik, A, Alqahtani, S, Baraka, D, Harthi, FA, Alsolm, E, Safieh, LA, Alowayn, AM, Alqubaishi, F, Mutairi, AA, Mangul, S, Almutairi, M, Aljawini, N, Albesher, N, Arabi, YM, Mahmoud, ES, Khattab, AK, Halawani, RT, Alahmadey, ZZ, Albakri, JK, Felemban, WA, Suliman, BA, Hasanato, R, Al-Awdah, L, Alghamdi, J, AlZahrani, D, AlJohani, S, Al-Afghani, H, AlDhawi, N, AlBardis, H, Alkwai, S, Alswailm, M, Almalki, F, Albeladi, M, Almohammed, I, Barhoush, E, Albader, A, Alotaibi, S, Alghamdi, B, Jung, J, fawzy, MS, Alrashed, M, Zeberg, H, Frithiof, R, Hultström, M, Lipcsey, M, Tardif, N, Rooyackers, O, Grip, J, Maricic, T, Helgeland, Ø, Magnus, P, Trogstad, L-IS, Lee, Y, Harris, JR, Mangino, M, Spector, TD, Emma, D, Moutsianas, L, Caulfield, MJ, Scott, RH, Kousathanas, A, Pasko, D, Walker, S, Stuckey, A, Odhams, CA, Rhodes, D, Fowler, T, Rendon, A, Chan, G, Arumugam, P, Karczewski, KJ, Martin, AR, Wilson, DJ, Spencer, CCA, Crook, DW, Wyllie, DH, O’Connell, AM, Atkinson, EG, Tsuo, K, Baya, N, Turley, P, Gupta, R, Walters, RK, Palmer, DS, Sarma, G, Cheng, N, Lu, W, Churchhouse, C, Goldstein, JI, King, D, Seed, C, Daly, MJ, Finucane, H, Bryant, S, Satterstrom, FK, Band, G, Earle, SG, Lin, S-K, Arning, N, Koelling, N, Armstrong, J, Rudkin, JK, Callier, S, Cusick, C, Soranzo, N, Zhao, JH, Danesh, J, Angelantonio, ED, Butterworth, AS, Sun, YV, Huffman, JE, Cho, K, O’Donnell, CJ, Tsao, P, Gaziano, JM, Peloso, G, Ho, Y-L, Smieszek, SP, Polymeropoulos, C, Polymeropoulos, V, Polymeropoulos, MH, Przychodzen, BP, Fernandez-Cadenas, I, Planas, AM, Perez-Tur, J, Llucià-Carol, L, Cullell, N, Muiño, E, Cárcel-Márquez, J, DeDiego, ML, Iglesias, LL, Soriano, A, Rico, V, Agüero, D, Bedini, JL, Lozano, F, Domingo, C, Robles, V, Ruiz-Jaén, F, Márquez, L, Gomez, J, Coto, E, Albaiceta, GM, García-Clemente, M, Dalmau, D, Arranz, MJ, Dietl, B, Serra-Llovich, A, Soler, P, Colobrán, R, Martín-Nalda, A, Martínez, AP, Bernardo, D, Rojo, S, Fiz-López, A, Arribas, E, de la Cal-Sabater, P, Segura, T, González-Villa, E, Serrano-Heras, G, Martí-Fàbregas, J, Jiménez-Xarrié, E, de Felipe Mimbrera, A, Masjuan, J, García-Madrona, S, Domínguez-Mayoral, A, Villalonga, JM, Menéndez-Valladares, P, Chasman, DI, Sesso, HD, Manson, JE, Buring, JE, Ridker, PM, Franco, G, Davis, L, Lee, S, Priest, J, Sankaran, VG, van Heel, D, Biesecker, L, Kerchberger, VE, Baillie, JK, Pathak, Gita A., Karjalainen, Juha, Stevens, Christine, Neale, Benjamin M., Daly, Mark, Ganna, Andrea, Andrews, Shea J., Kanai, Masahiro, Cordioli, Mattia, Polimanti, Renato, Harerimana, Nadia, Pirinen, Matti, Liao, Rachel G., Chwialkowska, Karolina, Trankiem, Amy, Balaconis, Mary K., Nguyen, Huy, Solomonson, Matthew, Veerapen, Kumar, Wolford, Brooke, Roberts, Genevieve, Park, Danny, Ball, Catherine A., Coignet, Marie, McCurdy, Shannon, Knight, Spencer, Partha, Raghavendran, Rhead, Brooke, Zhang, Miao, Berkowitz, Nathan, Gaddis, Michael, Noto, Keith, Ruiz, Luong, Pavlovic, Milo, Hong, Eurie L., Rand, Kristin, Girshick, Ahna, Guturu, Harendra, Baltzell, Asher Haug, Niemi, Mari E. K., Rahmouni, Souad, Guntz, Julien, Beguin, Yve, Pigazzini, Sara, Nkambule, Lindokuhle, Georges, Michel, Moutschen, Michel, Misset, Benoit, Darcis, Gille, Guiot, Julien, Azarzar, Samira, Gofflot, Stéphanie, Claassen, Sabine, Malaise, Olivier, Huynen, Pascale, Meuris, Christelle, Thys, Marie, Jacques, Jessica, Léonard, Philippe, Frippiat, Frederic, Giot, Jean-Baptiste, Sauvage, Anne-Sophie, Frenckell, Christian Von, Belhaj, Yasmine, Lambermont, Bernard, Nakanishi, Tomoko, Morrison, David R., Mooser, Vincent, Richards, J. Brent, Butler-Laporte, Guillaume, Forgetta, Vincenzo, Li, Rui, Ghosh, Biswarup, Laurent, Laetitia, Belisle, Alexandre, Henry, Danielle, Abdullah, Tala, Adeleye, Olumide, Mamlouk, Noor, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Vulesevic, Branka, Bouab, Meriem, Guzman, Charlotte, Petitjean, Loui, Tselios, Chri, Xue, Xiaoqing, Afilalo, Jonathan, Afilalo, Marc, Oliveira, Maureen, Brenner, Bluma, Brassard, Nathalie, Durand, Madeleine, Schurr, Erwin, Lepage, Pierre, Ragoussis, Jianni, Auld, Daniel, Chassé, Michaël, Kaufmann, Daniel E., Lathrop, G. Mark, Adra, Darin, Hayward, Caroline, Glessner, Joseph T., Shaw, Douglas M., Campbell, Archie, Morris, Marcela, Hakonarson, Hakon, Porteous, David J., Below, Jennifer, Richmond, Anne, Chang, Xiao, Polikowski, Hannah, Lauren, Petty E., Chen, Hung-Hsin, Wanying, Zhu, Fawns-Ritchie, Chloe, North, Kari, McCormick, Joseph B., Glessner, Joseph R., Gignoux, Christopher R., Wicks, Stephen J., Crooks, Kristy, Barnes, Kathleen C., Daya, Michelle, Shortt, Jonathan, Rafaels, Nichola, Chavan, Sameer, Timmers, Paul R. H. J., Wilson, James F., Tenesa, Albert, Kerr, Shona M., D’Mellow, Kenton, Shahin, Doaa, El-Sherbiny, Yasser M., von Hohenstaufen, Kathrin Aprile, Sobh, Ali, Eltoukhy, Madonna M., Nkambul, Lindokuhle, Elhadidy, Tamer A., Abd Elghafar, Mohamed S., El-Jawhari, Jehan J., Mohamed, Attia A. S., Elnagdy, Marwa H., Samir, Amr, Abdel-Aziz, Mahmoud, Khafaga, Walid T., El-Lawaty, Walaa M., Torky, Mohamed S., El-shanshory, Mohamed R., Yassen, Amr M., Hegazy, Mohamed A. F., Okasha, Kamal, Eid, Mohammed A., Moahmed, Hanteera S., Medina-Gomez, Carolina, Ikram, M. Arfan, Uitterlinden, Andre G., Mägi, Reedik, Milani, Lili, Metspalu, Andre, Laisk, Triin, Läll, Kristi, Lepamets, Maarja, Esko, Tõnu, Reimann, Ene, Naaber, Paul, Laane, Edward, Pesukova, Jaana, Peterson, Pärt, Kisand, Kai, Tabri, Jekaterina, Allos, Raili, Hensen, Kati, Starkopf, Joel, Ringmets, Inge, Tamm, Anu, Kallaste, Anne, Alavere, Helene, Metsalu, Kristjan, Puusepp, Mairo, Batini, Chiara, Tobin, Martin D., Venn, Laura D., Lee, Paul H., Shrine, Nick, Williams, Alexander T., Guyatt, Anna L., John, Catherine, Packer, Richard J., Ali, Altaf, Free, Robert C., Wang, Xueyang, Wain, Louise V., Hollox, Edward J., Bee, Catherine E., Adams, Emma L., Palotie, Aarno, Ripatti, Samuli, Ruotsalainen, Sanni, Kristiansson, Kati, Koskelainen, Sami, Perola, Marku, Donner, Kati, Kivinen, Katja, Kaunisto, Mari, Rivolta, Carlo, Bochud, Pierre-Yve, Bibert, Stéphanie, Boillat, Noémie, Nussle, Semira Gonseth, Albrich, Werner, Quinodoz, Mathieu, Kamdar, Dhryata, Suh, Noémie, Neofytos, Dionysio, Erard, Véronique, Voide, Cathy, Friolet, R., Vollenweider, P., Pagani, J. L., Oddo, M., zu Bentrup, F. Meyer, Conen, A., Clerc, O., Marchetti, O., Guillet, A., Guyat-Jacques, C., Foucras, S., Rime, M., Chassot, J., Jaquet, M., Viollet, R. Merlet, Lannepoudenx, Y., Portopena, L., Bochud, P. Y., Desgranges, F., Filippidis, P., Guéry, B., Haefliger, D., Kampouri, E. E., Manuel, O., Munting, A., Papadimitriou-Olivgeris, M., Regina, J., Rochat-Stettler, L., Suttels, V., Tadini, E., Tschopp, J., Van Singer, M., Viala, B., Boillat-Blanco, N., Brahier, T., Hügli, O., Meuwly, J. Y., Pantet, O., Gonseth Nussle, S., Bochud, M., D’Acremont, V., Estoppey Younes, S., Albrich, W. C., Suh, N., Cerny, A., O’Mahony, L., von Mering, C., Frischknecht, M., Kleger, G-R., Filipovic, M., Kahlert, C. R., Wozniak, H., Negro, T. Rochat, Pugin, J., Bouras, K., Knapp, C., Egger, T., Perret, A., Montillier, P., di Bartolomeo, C., Barda, B., de Cid, Rafael, Carreras, Anna, Moreno, Victor, Kogevinas, Manoli, Galván-Femenía, Iván, Blay, Natalia, Farré, Xavier, Sumoy, Lauro, Cortés, Beatriz, Mercader, Josep Maria, Guindo-Martinez, Marta, Torrents, David, Garcia-Aymerich, Judith, Castaño-Vinyals, Gemma, Dobaño, Carlota, Gori, Marco, Renieri, Alessandra, Mari, Francesca, Mondelli, Mario Umberto, Castelli, Francesco, Vaghi, Massimo, Rusconi, Stefano, Montagnani, Francesca, Bargagli, Elena, Franchi, Federico, Mazzei, Maria Antonietta, Cantarini, Luca, Tacconi, Danilo, Feri, Marco, Scala, Raffaele, Spargi, Genni, Nencioni, Cesira, Bandini, Maria, Caldarelli, Gian Piero, Canaccini, Anna, Ognibene, Agostino, D’Arminio Monforte, Antonella, Girardis, Massimo, Antinori, Andrea, Francisci, Daniela, Schiaroli, Elisabetta, Scotton, Pier Giorgio, Panese, Sandro, Scaggiante, Renzo, Monica, Matteo Della, Capasso, Mario, Fiorentino, Giuseppe, Castori, Marco, Aucella, Filippo, Biagio, Antonio Di, Masucci, Luca, Valente, Serafina, Mandalà, Marco, Zucchi, Patrizia, Giannattasio, Ferdinando, Coviello, Domenico A., Mussini, Cristina, Tavecchia, Luisa, Crotti, Lia, Rizzi, Marco, Rovere, Maria Teresa La, Sarzi-Braga, Simona, Bussotti, Maurizio, Ravaglia, Sabrina, Artuso, Rosangela, Perrella, Antonio, Romani, Davide, Bergomi, Paola, Catena, Emanuele, Vincenti, Antonella, Ferri, Claudio, Grassi, Davide, Pessina, Gloria, Tumbarello, Mario, Pietro, Massimo Di, Sabrina, Ravaglia, Luchi, Sauro, Furini, Simone, Dei, Simona, Benetti, Elisa, Picchiotti, Nicola, Sanarico, Maurizio, Ceri, Stefano, Pinoli, Pietro, Raimondi, Francesco, Biscarini, Filippo, Stella, Alessandra, Zguro, Kristina, Capitani, Katia, Tanfoni, Marco, Fallerini, Chiara, Daga, Sergio, Baldassarri, Margherita, Fava, Francesca, Frullanti, Elisa, Valentino, Floriana, Doddato, Gabriella, Giliberti, Annarita, Tita, Rossella, Amitrano, Sara, Bruttini, Mirella, Croci, Susanna, Meloni, Ilaria, Mencarelli, Maria Antonietta, Rizzo, Caterina Lo, Pinto, Anna Maria, Beligni, Giada, Tommasi, Andrea, Sarno, Laura Di, Palmieri, Maria, Carriero, Miriam Lucia, Alaverdian, Diana, Busani, Stefano, Bruno, Raffaele, Vecchia, Marco, Belli, Mary Ann, Mantovani, Stefania, Ludovisi, Serena, Quiros-Roldan, Eugenia, Antoni, Melania Degli, Zanella, Isabella, Siano, Matteo, Emiliozzi, Arianna, Fabbiani, Massimiliano, Rossetti, Barbara, Bergantini, Laura, D’Alessandro, Miriana, Cameli, Paolo, Bennett, David, Anedda, Federico, Marcantonio, Simona, Scolletta, Sabino, Guerrini, Susanna, Conticini, Edoardo, Frediani, Bruno, Spertilli, Chiara, Donati, Alice, Guidelli, Luca, Corridi, Marta, Croci, Leonardo, Piacentini, Paolo, Desanctis, Elena, Cappelli, Silvia, Verzuri, Agnese, Anemoli, Valentina, Pancrazzi, Alessandro, Lorubbio, Maria, Miraglia, Federica Gaia, Venturelli, Sophie, Cossarizza, Andrea, Vergori, Alessandra, Gabrieli, Arianna, Riva, Agostino, Paciosi, Francesco, Andretta, Francesca, Gatti, Francesca, Parisi, Saverio Giuseppe, Baratti, Stefano, Piscopo, Carmelo, Russo, Roberta, Andolfo, Immacolata, Iolascon, Achille, Carella, Massimo, Merla, Giuseppe, Squeo, Gabriella Maria, Raggi, Pamela, Marciano, Carmen, Perna, Rita, Bassetti, Matteo, Sanguinetti, Maurizio, Giorli, Alessia, Salerni, Lorenzo, Parravicini, Pierpaolo, Menatti, Elisabetta, Trotta, Tullio, Coiro, Gabriella, Lena, Fabio, Martinelli, Enrico, Mancarella, Sandro, Gabbi, Chiara, Maggiolo, Franco, Ripamonti, Diego, Bachetti, Tiziana, Suardi, Claudia, Parati, Gianfranco, Bottà, Giordano, Domenico, Paolo Di, Rancan, Ilaria, Bianchi, Francesco, Colombo, Riccardo, Barbieri, Chiara, Acquilini, Donatella, Andreucci, Elena, Segala, Francesco Vladimiro, Tiseo, Giusy, Falcone, Marco, Lista, Mirjam, Poscente, Monica, Vivo, Oreste De, Petrocelli, Paola, Guarnaccia, Alessandra, Baroni, Silvia, van Heel, David A., Hunt, Karen A., Trembath, Richard C., Huang, Qin Qin, Martin, Hilary C., Mason, Dan, Trivedi, Bhavi, Wright, John, Finer, Sarah, Akhtar, Shaheen, Anwar, Mohammad, Arciero, Elena, Ashraf, Samina, Breen, Gerome, Chung, Raymond, Curtis, Charles J., Chowdhury, Maharun, Colligan, Grainne, Deloukas, Pano, Durham, Ceri, Griffiths, Chri, Hurles, Matt, Hussain, Shapna, Islam, Kamrul, Khan, Ahsan, Khan, Amara, Lavery, Cath, Lee, Sang Hyuck, Lerner, Robin, MacArthur, Daniel, MacLaughlin, Bev, Martin, Hilary, Miah, Shefa, Newman, Bill, Safa, Nishat, Tahmasebi, Farah, Griffiths, Christopher J., Smith, Albert V., Boughton, Andrew P., Li, Kevin W., LeFaive, Jonathon, Annis, Aubrey, Niavarani, Ahmadreza, Aliannejad, Rasoul, Sharififard, Bahareh, Amirsavadkouhi, Ali, Naderpour, Zeinab, Tadi, Hengameh Ansari, Aleagha, Afshar Etemadi, Ahmadi, Saeideh, Moghaddam, Seyed Behrooz Mohseni, Adamsara, Alireza, Saeedi, Morteza, Abdollahi, Hamed, Hosseini, Abdolmajid, Chariyavilaskul, Pajaree, Jantarabenjakul, Watsamon, Hirankarn, Nattiya, Chamnanphon, Monpat, Suttichet, Thitima B., Shotelersuk, Vorasuk, Pongpanich, Monnat, Phokaew, Chureerat, Chetruengchai, Wanna, Putchareon, Opa, Torvorapanit, Pattama, Puthanakit, Thanyawee, Suchartlikitwong, Pintip, Nilaratanakul, Voraphoj, Sodsai, Pimpayao, Brumpton, Ben M., Hveem, Kristian, Willer, Cristen, Zhou, Wei, Rogne, Tormod, Solligard, Erik, Åsvold, Bjørn Olav, Franke, Lude, Boezen, Marike, Deelen, Patrick, Claringbould, Annique, Lopera, Esteban, Warmerdam, Robert, Vonk, Judith. M., van Blokland, Irene, Lanting, Pauline, Ori, Anil P. S., Feng, Yen-Chen Anne, Mercader, Josep, Weiss, Scott T., Karlson, Elizabeth W., Smoller, Jordan W., Murphy, Shawn N., Meigs, James B., Woolley, Ann E., Green, Robert C., Perez, Emma F., Zöllner, Sebastian, Wang, Jiongming, Beck, Andrew, Sloofman, Laura G., Ascolillo, Steven, Sebra, Robert P., Collins, Brett L., Levy, Te, Buxbaum, Joseph D., Sealfon, Stuart C., Jordan, Daniel M., Thompson, Ryan C., Gettler, Kyle, Chaudhary, Kumardeep, Belbin, Gillian M., Preuss, Michael, Hoggart, Clive, Choi, Sam, Underwood, Slayton J., Salib, Irene, Britvan, Bari, Keller, Katherine, Tang, Lara, Peruggia, Michael, Hiester, Liam L., Niblo, Kristi, Aksentijevich, Alexandra, Labkowsky, Alexander, Karp, Avromie, Zlatopolsky, Menachem, Zyndorf, Marissa, Charney, Alexander W., Beckmann, Noam D., Schadt, Eric E., Abul-Husn, Noura S., Cho, Judy H., Itan, Yuval, Kenny, Eimear E., Loos, Ruth J. F., Nadkarni, Girish N., Do, Ron, O’Reilly, Paul, Huckins, Laura M., Ferreira, Manuel A. R., Abecasis, Goncalo R., Leader, Joseph B., Cantor, Michael N., Justice, Anne E., Carey, Dave J., Chittoor, Geetha, Josyula, Navya Shilpa, Kosmicki, Jack A., Horowitz, Julie E., Baras, Ari, Gass, Matthew C., Yadav, Ashish, Mirshahi, Tooraj, Hottenga, Jouke Jan, Bartels, Meike, de geus, Eco E. J. C., Nivard, Michel M. G., Verma, Anurag, Ritchie, Marylyn D., Rader, Daniel, Li, Binglan, Verma, Shefali S., Lucas, Anastasia, Bradford, Yuki, Abedalthagafi, Malak, Alaamery, Manal, Alshareef, Abdulraheem, Sawaji, Mona, Massadeh, Salam, AlMalik, Abdulaziz, Alqahtani, Saleh, Baraka, Dona, Harthi, Fawz Al, Alsolm, Ebtehal, Safieh, Leen Abu, Alowayn, Albandary M., Alqubaishi, Fatimah, Mutairi, Amal Al, Mangul, Serghei, Almutairi, Mansour, Aljawini, Nora, Albesher, Nour, Arabi, Yaseen M., Mahmoud, Ebrahim S., Khattab, Amin K., Halawani, Roaa T., Alahmadey, Ziab Z., Albakri, Jehad K., Felemban, Walaa A., Suliman, Bandar A., Hasanato, Rana, Al-Awdah, Laila, Alghamdi, Jahad, AlZahrani, Deema, AlJohani, Sameera, Al-Afghani, Hani, AlDhawi, Nouf, AlBardis, Hadeel, Alkwai, Sarah, Alswailm, Moneera, Almalki, Faisal, Albeladi, Maha, Almohammed, Iman, Barhoush, Eman, Albader, Anoud, Alotaibi, Sara, Alghamdi, Bader, Jung, Junghyun, fawzy, Mohammad S., Alrashed, May, Zeberg, Hugo, Nkambul, Lindo, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklo, Tardif, Nicola, Rooyackers, Olav, Grip, Jonathan, Maricic, Tomislav, Helgeland, Øyvind, Magnus, Per, Trogstad, Lill-Iren S., Lee, Yunsung, Harris, Jennifer R., Mangino, Massimo, Spector, Tim D., Emma, Duncan, Moutsianas, Louka, Caulfield, Mark J., Scott, Richard H., Kousathanas, Athanasio, Pasko, Dorota, Walker, Susan, Stuckey, Alex, Odhams, Christopher A., Rhodes, Daniel, Fowler, Tom, Rendon, Augusto, Chan, Georgia, Arumugam, Prabhu, Karczewski, Konrad J., Martin, Alicia R., Wilson, Daniel J., Spencer, Chris C. A., Crook, Derrick W., Wyllie, David H., O’Connell, Anne Marie, Atkinson, Elizabeth G., Tsuo, Kristin, Baya, Nikola, Turley, Patrick, Gupta, Rahul, Walters, Raymond K., Palmer, Duncan S., Sarma, Gopal, Cheng, Nathan, Lu, Wenhan, Churchhouse, Claire, Goldstein, Jacqueline I., King, Daniel, Seed, Cotton, Daly, Mark J., Finucane, Hilary, Bryant, Sam, Satterstrom, F. Kyle, Band, Gavin, Earle, Sarah G., Lin, Shang-Kuan, Arning, Nicola, Koelling, Nil, Armstrong, Jacob, Rudkin, Justine K., Callier, Shawneequa, Cusick, Caroline, Soranzo, Nicole, Zhao, Jing Hua, Danesh, John, Angelantonio, Emanuele Di, Butterworth, Adam S., Sun, Yan V., Huffman, Jennifer E., Cho, Kelly, O’Donnell, Christopher J., Tsao, Phil, Gaziano, J. Michael, Peloso, Gina, Ho, Yuk-Lam, Smieszek, Sandra P., Polymeropoulos, Christo, Polymeropoulos, Vasilio, Polymeropoulos, Mihael H., Przychodzen, Bartlomiej P., Fernandez-Cadenas, Israel, Planas, Anna M., Perez-Tur, Jordi, Llucià-Carol, Laia, Cullell, Natalia, Muiño, Elena, Cárcel-Márquez, Jara, DeDiego, Marta L., Iglesias, Lara Lloret, Soriano, Alex, Rico, Veronica, Agüero, Daiana, Bedini, Josep L., Lozano, Francisco, Domingo, Carlo, Robles, Veronica, Ruiz-Jaén, Francisca, Márquez, Leonardo, Gomez, Juan, Coto, Eliecer, Albaiceta, Guillermo M., García-Clemente, Marta, Dalmau, David, Arranz, Maria J., Dietl, Beatriz, Serra-Llovich, Alex, Soler, Pere, Colobrán, Roger, Martín-Nalda, Andrea, Martínez, Alba Parra, Bernardo, David, Rojo, Silvia, Fiz-López, Aida, Arribas, Elisa, de la Cal-Sabater, Paloma, Segura, Tomá, González-Villa, Esther, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Jiménez-Xarrié, Elena, de Felipe Mimbrera, Alicia, Masjuan, Jaime, García-Madrona, Sebastian, Domínguez-Mayoral, Anna, Villalonga, Joan Montaner, Menéndez-Valladares, Paloma, Chasman, Daniel I., Sesso, Howard D., Manson, JoAnn E., Buring, Julie E., Ridker, Paul M., Franco, Giulianini, Davis, Lea, Lee, Sulggi, Priest, Jame, Sankaran, Vijay G., van Heel, David, Biesecker, Le, Kerchberger, V. Eric, Baillie, J. Kenneth, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Biological Psychology, APH - Mental Health, AMS - Sports, AMS - Ageing & Vitality, APH - Methodology, Mccurdy, Shannon, Mccormick, Joseph B., Macarthur, Daniel, Maclaughlin, Bev, Lefaive, Jonathon, Almalik, Abdulaziz, Alzahrani, Deema, Aljohani, Sameera, Aldhawi, Nouf, Albardis, Hadeel, Fawzy, Mohammad S., Dediego, Marta L., Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), University of Zurich, COVID-19 Host Genetics Initiative, Barcelona Supercomputing Center, COVID-19 Genetics Initiative, including authors, Institute for Molecular Medicine Finland, and Data Science Genetic Epidemiology Lab

Subjects
Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC], Quantitative Trait Loci, MUC5B PROMOTER POLYMORPHISM, Genome-wide association studies, COVID-19 (Malaltia), UFSP13-7 Evolution in Action: From Genomes to Ecosystems, COVID-19 (Disease), Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, SDG 3 - Good Health and Well-being, Humans, genetics, Genetic variation, Genomes, Medicinsk genetik, 1000 Multidisciplinary, Multidisciplinary, Chromosome Mapping, COVID-19, Human Genetics, 10124 Institute of Molecular Life Sciences, covid-19, 3121 General medicine, internal medicine and other clinical medicine, 570 Life sciences, biology, Medical Genetics
Abstract

Matters arising from: Mapping the human genetic architecture of COVID-19 Original Article published on 08 July 2021 https://www.nature.com/articles/s41586-021-03767-x The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity. Here we present meta-analyses bringing together 60 studies from 25 countries (Fig. 1 and Supplementary Table 1) for three COVID-19-related phenotypes: (1) individuals critically ill with COVID-19 on the basis of requiring respiratory support in hospital or who died as a consequence of the disease (9,376 cases, of which 3,197 are new in this data release, and 1,776,645 control individuals); (2) individuals with moderate or severe COVID-19 defined as those hospitalized due to symptoms associated with the infection (25,027 cases, 11,386 new and 2,836,272 control individuals); and (3) all cases with reported SARS-CoV-2 infection regardless of symptoms (125,584 cases, 76,022 new and 2,575,347 control individuals). Most studies have reported results before the roll out of the COVID-19 vaccination campaign. An overview of the study design is provided in Supplementary Fig. 1. We found a total of 23 genome-wide significant loci (P

Published
2022

42. Assessing the prognostic value of tumor-infiltrating CD57+ cells in advanced stage head and neck cancer using QuPath digital image analysis

Author

Emma J. de Ruiter, Sangeeta K. Bisheshar, Reinout H. de Roest, Frederik W. R. Wesseling, Frank J. P. Hoebers, Mari F. C. M. van den Hout, C. René Leemans, Ruud H. Brakenhoff, Remco de Bree, Chris H. J. Terhaard, Stefan M. Willems, Radiotherapie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: DA Pat Pathologie (9), RS: GROW - R2 - Basic and Translational Cancer Biology, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Otolaryngology / Head & Neck Surgery, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, and General practice

Subjects
LYMPHOCYTES PREDICT, Head and neck squamous cell carcinoma (HNSCC), Cell Biology, General Medicine, NK cells, NEOADJUVANT CHEMORADIOTHERAPY, PERIPHERAL-BLOOD, Pathology and Forensic Medicine, Prognostic biomarkers, QuPath, Digital pathology, SQUAMOUS-CELL CARCINOMA, CD8(+), Molecular Biology, CD57, Tumor-infiltrating lymphocytes (TILs)
Abstract

This study aimed to assess the prognostic value of intratumoral CD57+ cells in head and neck squamous cell carcinoma (HNSCC) and to examine the reproducibility of these analyses using QuPath. Pretreatment biopsies of 159 patients with HPV-negative, stage III/IV HNSCC treated with chemoradiotherapy were immunohistochemically stained for CD57. The number of CD57+ cells per mm2 tumor epithelium was quantified by two independent observers and by QuPath, software for digital pathology image analysis. Concordance between the observers and QuPath was assessed by intraclass correlation coefficients (ICC). The correlation between CD57 and clinicopathological characteristics was assessed; associations with clinical outcome were estimated using Cox proportional hazard analysis and visualized using Kaplan-Meier curves. The patient cohort had a 3-year OS of 65.8% with a median follow-up of 54 months. The number of CD57+ cells/mm2 tumor tissue did not correlate to OS, DFS, or LRC. N stage predicted prognosis (OS: HR 0.43, p = 0.008; DFS: HR 0.41, p = 0.003; LRC: HR 0.24, p = 0.007), as did WHO performance state (OS: HR 0.48, p = 0.028; LRC: 0.33, p = 0.039). Quantification by QuPath showed moderate to good concordance with two human observers (ICCs 0.836, CI 0.805–0.863, and 0.741, CI 0.692–0.783, respectively). In conclusion, the presence of CD57+ TILs did not correlate to prognosis in advanced stage, HPV-negative HNSCC patients treated with chemoradiotherapy. Substantial concordance between human observers and QuPath was found, confirming a promising future role for digital, algorithm driven image analysis.

Published
2022

43. Molecular characterization of an embryonal rhabdomyosarcoma occurring in a patient with Kabuki syndrome: report and literature review in the light of tumor predisposition syndromes

Author

Sietse M. Aukema, Selina Glaser, Mari F. C. M. van den Hout, Sonja Dahlum, Marinus J. Blok, Morten Hillmer, Julia Kolarova, Raf Sciot, Dina A. Schott, Reiner Siebert, and Constance T. R. M. Stumpel

Subjects
GENETIC LANDSCAPE, Cancer Research, Kabuki syndrome, CHILDHOOD-CANCER, KMT2D, DNA, UNIPARENTAL DISOMY, Methylation, CLONAL EVOLUTION, GENOMIC ANALYSIS, PEDIATRIC CANCER PREDISPOSITION, Oncology, KDM6A MUTATIONS, Tumor predisposition, Rhabdomyosarcoma, METHYLTRANSFERASE KMT2D SUSTAINS, Genetics, NON-HODGKIN-LYMPHOMA, Genetics (clinical)
Abstract

Kabuki syndrome is a well-recognized syndrome characterized by facial dysmorphism and developmental delay/intellectual disability and in the majority of patients a germline variant in KMT2D is found. As somatic KMT2D variants can be found in 5–10% of tumors a tumor predisposition in Kabuki syndrome is discussed. So far less than 20 patients with Kabuki syndrome and a concomitant malignancy have been published. Here we report on a female patient with Kabuki syndrome and a c.2558_2559delCT germline variant in KMT2D who developed an embryonal rhabdomyosarcoma (ERMS) at 10 years. On tumor tissue we performed DNA-methylation profiling and exome sequencing (ES). Copy number analyses revealed aneuploidies typical for ERMS including (partial) gains of chromosomes 2, 3, 7, 8, 12, 15, and 20 and 3 focal deletions of chromosome 11p. DNA methylation profiling mapped the case to ERMS by a DNA methylation-based sarcoma classifier. Sequencing suggested gain of the wild-type KMT2D allele in the trisomy 12. Including our patient literature review identified 18 patients with Kabuki syndrome and a malignancy. Overall, the landscape of malignancies in patients with Kabuki syndrome was reminiscent of that of the pediatric population in general. Histopathological and molecular data were only infrequently reported and no report included next generation sequencing and/or DNA-methylation profiling. Although we found no strong arguments pointing towards KS as a tumor predisposition syndrome, based on the small numbers any relation cannot be fully excluded. Further planned studies including profiling of additional tumors and long term follow-up of KS-patients into adulthood could provide further insights.

Published
2022

46. Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Author

Sheppard, S.E., Bryant, L., Wickramasekara, R.N., Vaccaro, C., Robertson, B., Hallgren, J., Hulen, J., Watson, C.J., Faundes, V., Duffourd, Y., Lee, P., Simon, M.C., Cruz, X. de la, Padilla, N., Flores-Mendez, M., Akizu, N., Smiler, J., Pellegrino Da Silva, R., Li, D., March, M., Diaz-Rosado, A., Peixoto de Barcelos, I., Choa, Z.X., Lim, C.Y., Dubourg, C., Journel, H., Demurger, F., Mulhern, M., Akman, C., Lippa, N., Andrews, M., Baldridge, D., Constantino, J., Haeringen, A. van, Snoeck-Streef, I., Chow, P., Hing, A., Graham Jr, J.M., Au, M., Faivre, L., Shen, W., Mao, R., Palumbos, J., Viskochil, D., Gahl, W., Tifft, C., Macnamara, E., Hauser, N., Miller, R., Maffeo, J., Afenjar, A., Doummar, D., Keren, B., Arn, P., Macklin-Mantia, S., Meerschaut, I., Callewaert, B., Reis, A., Zweier, C., Brewer, C., Saggar, A., Smeland, M.F., Kumar, Ajith, Elmslie, F., Deshpande, C., Nizon, M., Cogne, B., Ierland, Y. van, Wilke, M., Slegtenhorst, M. van, Koudijs, S., Chen, J.Y., Dredge, D., Pier, D., Wortmann, S.B., Kamsteeg, E.J., Koch, J., Haynes, D., Pollack, L., Titheradge, H., Ranguin, K., Denommé-Pichon, A.S., Weber, S., Perez de la Fuente, R., Sanchez Del Pozo, J., Lezana Rosales, J.M., Joset, P., Steindl, K., Rauch, A., Mei, D., Mari, F., Guerrini, R., Lespinasse, J., Tran Mau-Them, F., Philippe, C., Dauriat, B., Raymond, L., Moutton, S., Cueto-González, A.M., Tan, T.Y., Mignot, C., Grotto, S., Renaldo, F., Drivas, T.G., Hennessy, L., Raper, A., Parenti, I., Kaiser, F.J., Kuechler, A., Busk, Ø.L., Islam, L., Siedlik, J.A., Henderson, L.B., Juusola, J., Person, R., Schnur, R.E., Vitobello, A., Banka, S., Bhoj, E.J., Stessman, H.A.F., Sheppard, S.E., Bryant, L., Wickramasekara, R.N., Vaccaro, C., Robertson, B., Hallgren, J., Hulen, J., Watson, C.J., Faundes, V., Duffourd, Y., Lee, P., Simon, M.C., Cruz, X. de la, Padilla, N., Flores-Mendez, M., Akizu, N., Smiler, J., Pellegrino Da Silva, R., Li, D., March, M., Diaz-Rosado, A., Peixoto de Barcelos, I., Choa, Z.X., Lim, C.Y., Dubourg, C., Journel, H., Demurger, F., Mulhern, M., Akman, C., Lippa, N., Andrews, M., Baldridge, D., Constantino, J., Haeringen, A. van, Snoeck-Streef, I., Chow, P., Hing, A., Graham Jr, J.M., Au, M., Faivre, L., Shen, W., Mao, R., Palumbos, J., Viskochil, D., Gahl, W., Tifft, C., Macnamara, E., Hauser, N., Miller, R., Maffeo, J., Afenjar, A., Doummar, D., Keren, B., Arn, P., Macklin-Mantia, S., Meerschaut, I., Callewaert, B., Reis, A., Zweier, C., Brewer, C., Saggar, A., Smeland, M.F., Kumar, Ajith, Elmslie, F., Deshpande, C., Nizon, M., Cogne, B., Ierland, Y. van, Wilke, M., Slegtenhorst, M. van, Koudijs, S., Chen, J.Y., Dredge, D., Pier, D., Wortmann, S.B., Kamsteeg, E.J., Koch, J., Haynes, D., Pollack, L., Titheradge, H., Ranguin, K., Denommé-Pichon, A.S., Weber, S., Perez de la Fuente, R., Sanchez Del Pozo, J., Lezana Rosales, J.M., Joset, P., Steindl, K., Rauch, A., Mei, D., Mari, F., Guerrini, R., Lespinasse, J., Tran Mau-Them, F., Philippe, C., Dauriat, B., Raymond, L., Moutton, S., Cueto-González, A.M., Tan, T.Y., Mignot, C., Grotto, S., Renaldo, F., Drivas, T.G., Hennessy, L., Raper, A., Parenti, I., Kaiser, F.J., Kuechler, A., Busk, Ø.L., Islam, L., Siedlik, J.A., Henderson, L.B., Juusola, J., Person, R., Schnur, R.E., Vitobello, A., Banka, S., Bhoj, E.J., and Stessman, H.A.F.

Abstract

Item does not contain fulltext, Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems.

Published
2023

48. ConNet: Designing a Fast, Efficient, and Robust Crowd Counting Model Through Composite Compression

Author

Regina Marie A. Masilang, Bianca Joy R. Benedictos, Mikayla M. Tejada, Giann Jericho Mari F. Marasigan, and Arren Matthew C. Antioquia

Subjects
Artificial Intelligence, Computer Vision and Pattern Recognition, Software
Abstract

Counting the number of people in a specific area is crucial in maintaining proper crowd safety and management especially in highly-congested indoor scenarios. Recent convolutional neural network (CNN) approaches integrate auxiliary sub-networks to increase the accuracy of the model in estimating crowd size. However, these models require large computational costs due to additional calculations, resulting in an impractically slow inference speed for real-world applications. In this paper, we propose a fast, efficient, and robust crowd counting model called Condensed Network or ConNet. We utilize a composite technique composed of multiple compression methods to reduce the number of parameters of our proposed model. ConNet attains counting accuracy on par with state-of-the-art crowd counting methods on benchmark datasets featuring indoor scenes, while significantly reducing parameter count and increasing inference speed. Moreover, ConNet still performs accurately even with extreme changes in lighting conditions, image resolutions, and camera orientations. Our smallest model ConNet-04 has 61.0[Formula: see text] less parameters and is at most 9.0[Formula: see text] faster than the baseline approach. Our code and trained models are publicly available at https://github.com/mikatej/ConNet.

Published
2023

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