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93 results on '"Sulem, P"'

1. Novel loci and biomedical consequences of iron homoeostasis variation

Author: Elias Allara, Steven Bell, Rebecca Smith, Spencer J. Keene, Dipender Gill, Liam Gaziano, Deisy Morselli Gysi, Feiyi Wang, Vinicius Tragante, Amy Mason, Savita Karthikeyan, R. Thomas Lumbers, Emmanuela Bonglack, Willem Ouwehand, David J. Roberts, Joseph Dowsett, Sisse Rye Ostrowski, Margit Hørup Larsen, Henrik Ullum, Ole Birger Pedersen, Søren Brunak, Karina Banasik, Christian Erikstrup, DBDS Genomic Consortium, Jonathan Mitchell, Christian Fuchsberger, Cristian Pattaro, Peter P. Pramstaller, Domenico Girelli, Mikko Arvas, Jarkko Toivonen, Sophie Molnos, Annette Peters, Ozren Polasek, Igor Rudan, Caroline Hayward, Ciara McDonnell, Nicola Pirastu, James F. Wilson, Katja van den Hurk, Franke Quee, Luigi Ferrucci, Stefania Bandinelli, Toshiko Tanaka, Giorgia Girotto, Maria Pina Concas, Alessandro Pecori, Niek Verweij, Pim van der Harst, Yordi J. van de Vegte, Lambertus A. Kiemeney, Fred C. Sweep, Tessel E. Galesloot, Patrick Sulem, Daniel Gudbjartsson, Egil Ferkingstad, FinnGen Consortium, Luc Djousse, Kelly Cho, Michael Inouye, Stephen Burgess, Beben Benyamin, Konrad Oexle, Dorine Swinkels, Kari Stefansson, Magnus Magnusson, Andrea Ganna, Michael Gaziano, Kerry Ivey, John Danesh, Alexandre Pereira, Angela M. Wood, Adam S. Butterworth, and Emanuele Di Angelantonio
Subjects: Biology (General), QH301-705.5
Abstract: Abstract Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported. Mapping to putative genes indicated involvement in iron-trait expression, erythropoiesis, immune response and cellular trafficking. Mendelian randomisation of 292 disease outcomes in 1,492,717 participants revealed associations of iron-related loci and iron status with selected health outcomes across multiple domains. These associations were largely driven by HFE, which was associated with the largest iron variation. Our findings enhance understanding of iron homoeostasis and its biomedical consequences, suggesting that lifelong exposure to higher iron levels is likely associated with lower risk of anaemia-related disorders and higher risk of genitourinary, musculoskeletal, infectious and neoplastic diseases.
Published: 2024
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2. Transformers significantly improve splice site prediction

Author: Benedikt A. Jónsson, Gísli H. Halldórsson, Steinþór Árdal, Sölvi Rögnvaldsson, Eyþór Einarsson, Patrick Sulem, Daníel F. Guðbjartsson, Páll Melsted, Kári Stefánsson, and Magnús Ö. Úlfarsson
Subjects: Biology (General), QH301-705.5
Abstract: Abstract Mutations that affect RNA splicing significantly impact human diversity and disease. Here we present a method using transformers, a type of machine learning model, to detect splicing from raw 45,000-nucleotide sequences. We generate embeddings with residual neural networks and apply hard attention to select splice site candidates, enabling efficient training on long sequences. Our method surpasses the leading tool, SpliceAI, in detecting splice sites in GENCODE and ENSEMBL annotations. Using extensive RNA sequencing data from an Icelandic cohort of 17,848 individuals and the Genotype-Tissue Expression (GTEx) project, our method demonstrates superior performance in detecting splice junctions compared to SpliceAI-10k (PR-AUC = 0.834 vs. PR-AUC = 0.820) and is more effective at identifying disease-related splice variants in ClinVar (PR-AUC = 0.997 vs. PR-AUC = 0.996). These advancements hold promise for improving genetic research and clinical diagnostics, potentially leading to better understanding and treatment of splicing-related diseases.
Published: 2024
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3. Sequence variants associated with BMI affect disease risk through BMI itself

Author: Gudmundur Einarsson, Gudmar Thorleifsson, Valgerdur Steinthorsdottir, Florian Zink, Hannes Helgason, Thorhildur Olafsdottir, Solvi Rognvaldsson, Vinicius Tragante, Magnus O. Ulfarsson, Gardar Sveinbjornsson, Audunn S. Snaebjarnarson, Hafsteinn Einarsson, Hildur M. Aegisdottir, Gudrun A. Jonsdottir, Anna Helgadottir, Solveig Gretarsdottir, Unnur Styrkarsdottir, Hannes K. Arnason, Ragnar Bjarnason, Emil Sigurdsson, David O. Arnar, Einar S. Bjornsson, Runolfur Palsson, Gyda Bjornsdottir, Hreinn Stefansson, Thorgeir Thorgeirsson, Patrick Sulem, Unnur Thorsteinsdottir, Hilma Holm, Daniel F. Gudbjartsson, and Kari Stefansson
Subjects: Science
Abstract: Abstract Mendelian Randomization studies indicate that BMI contributes to various diseases, but it’s unclear if this is entirely mediated by BMI itself. This study examines whether disease risk from BMI-associated sequence variants is mediated through BMI or other mechanisms, using data from Iceland and the UK Biobank. The associations of BMI genetic risk score with diseases like fatty liver disease, knee replacement, and glucose intolerance were fully attenuated when conditioned on BMI, and largely for type 2 diabetes, heart failure, myocardial infarction, atrial fibrillation, and hip replacement. Similar attenuation was observed for chronic kidney disease and stroke, though results varied. Findings were consistent across sexes, except for myocardial infarction. Residual effects may result from temporal BMI changes, pleiotropy, measurement error, non-linear relationships, non-collapsibility, or confounding. The attenuation extent of BMI genetic risk score on disease associations suggests the potential impact of reducing BMI on disease risk.
Published: 2024
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4. Sequence variants influencing the regulation of serum IgG subclass levels

Author: Thorunn A. Olafsdottir, Gudmar Thorleifsson, Aitzkoa Lopez de Lapuente Portilla, Stefan Jonsson, Lilja Stefansdottir, Abhishek Niroula, Aslaug Jonasdottir, Hannes P. Eggertsson, Gisli H. Halldorsson, Gudny E. Thorlacius, Asgeir O. Arnthorsson, Unnur S. Bjornsdottir, Folkert W. Asselbergs, Arthur E. H. Bentlage, Gudmundur I. Eyjolfsson, Steinunn Gudmundsdottir, Kristbjorg Gunnarsdottir, Bjarni V. Halldorsson, Hilma Holm, Bjorn R. Ludviksson, Pall Melsted, Gudmundur L. Norddahl, Isleifur Olafsson, Saedis Saevarsdottir, Olof Sigurdardottir, Asgeir Sigurdsson, Robin Temming, Pall T. Önundarson, Unnur Thorsteinsdottir, Gestur Vidarsson, Patrick Sulem, Daniel F. Gudbjartsson, Ingileif Jonsdottir, Björn Nilsson, and Kari Stefansson
Subjects: Science
Abstract: Abstract Immunoglobulin G (IgG) is the main isotype of antibody in human blood. IgG consists of four subclasses (IgG1 to IgG4), encoded by separate constant region genes within the Ig heavy chain locus (IGH). Here, we report a genome-wide association study on blood IgG subclass levels. Across 4334 adults and 4571 individuals under 18 years, we discover ten new and identify four known variants at five loci influencing IgG subclass levels. These variants also affect the risk of asthma, autoimmune diseases, and blood traits. Seven variants map to the IGH locus, three to the Fcγ receptor (FCGR) locus, and two to the human leukocyte antigen (HLA) region, affecting the levels of all IgG subclasses. The most significant associations are observed between the G1m (f), G2m(n) and G3m(b*) allotypes, and IgG1, IgG2 and IgG3, respectively. Additionally, we describe selective associations with IgG4 at 16p11.2 (ITGAX) and 17q21.1 (IKZF3, ZPBP2, GSDMB, ORMDL3). Interestingly, the latter coincides with a highly pleiotropic signal where the allele associated with lower IgG4 levels protects against childhood asthma but predisposes to inflammatory bowel disease. Our results provide insight into the regulation of antibody-mediated immunity that can potentially be useful in the development of antibody based therapeutics.
Published: 2024
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5. Loss-of-function variants in ITSN1 confer high risk of Parkinson’s disease

Author: Astros Th. Skuladottir, Vinicius Tragante, Gardar Sveinbjornsson, Hannes Helgason, Arni Sturluson, Anna Bjornsdottir, Palmi Jonsson, Vala Palmadottir, Olafur A. Sveinsson, Brynjar O. Jensson, Sigurjon A. Gudjonsson, Erna V. Ivarsdottir, Rosa S. Gisladottir, Arni F. Gunnarsson, G. Bragi Walters, Gudrun A. Jonsdottir, Thorgeir E. Thorgeirsson, Gyda Bjornsdottir, Hilma Holm, Daniel F. Gudbjartsson, Patrick Sulem, Hreinn Stefansson, and Kari Stefansson
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Parkinson’s disease (PD) is a debilitating neurodegenerative disorder and its rising global incidence highlights the need for the identification of modifiable risk factors. In a gene-based burden test of rare variants (8647 PD cases and 777,693 controls) we discovered a novel association between loss-of-function variants in ITSN1 and PD. This association was further supported with burden data from the Neurodegenerative Disease Knowledge Portal and the Accelerating Medicines Partnership Parkinson’s Disease Knowledge Platform. Our findings show that Rho GTPases and disruptions in synaptic vesicle transport may be involved in the pathogenesis of PD, pointing to the possibility of novel therapeutic approaches.
Published: 2024
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6. Deciphering the genetics and mechanisms of predisposition to multiple myeloma

Author: Molly Went, Laura Duran-Lozano, Gisli H. Halldorsson, Andrea Gunnell, Nerea Ugidos-Damboriena, Philip Law, Ludvig Ekdahl, Amit Sud, Gudmar Thorleifsson, Malte Thodberg, Thorunn Olafsdottir, Antton Lamarca-Arrizabalaga, Caterina Cafaro, Abhishek Niroula, Ram Ajore, Aitzkoa Lopez de Lapuente Portilla, Zain Ali, Maroulio Pertesi, Hartmut Goldschmidt, Lilja Stefansdottir, Sigurdur Y. Kristinsson, Simon N. Stacey, Thorvardur J. Love, Saemundur Rognvaldsson, Roman Hajek, Pavel Vodicka, Ulrika Pettersson-Kymmer, Florentin Späth, Carolina Schinke, Frits Van Rhee, Patrick Sulem, Egil Ferkingstad, Grimur Hjorleifsson Eldjarn, Ulf-Henrik Mellqvist, Ingileif Jonsdottir, Gareth Morgan, Pieter Sonneveld, Anders Waage, Niels Weinhold, Hauke Thomsen, Asta Försti, Markus Hansson, Annette Juul-Vangsted, Unnur Thorsteinsdottir, Kari Hemminki, Martin Kaiser, Thorunn Rafnar, Kari Stefansson, Richard Houlston, and Björn Nilsson
Subjects: Science
Abstract: Abstract Multiple myeloma (MM) is an incurable malignancy of plasma cells. Epidemiological studies indicate a substantial heritable component, but the underlying mechanisms remain unclear. Here, in a genome-wide association study totaling 10,906 cases and 366,221 controls, we identify 35 MM risk loci, 12 of which are novel. Through functional fine-mapping and Mendelian randomization, we uncover two causal mechanisms for inherited MM risk: longer telomeres; and elevated levels of B-cell maturation antigen (BCMA) and interleukin-5 receptor alpha (IL5RA) in plasma. The largest increase in BCMA and IL5RA levels is mediated by the risk variant rs34562254-A at TNFRSF13B. While individuals with loss-of-function variants in TNFRSF13B develop B-cell immunodeficiency, rs34562254-A exerts a gain-of-function effect, increasing MM risk through amplified B-cell responses. Our results represent an analysis of genetic MM predisposition, highlighting causal mechanisms contributing to MM development.
Published: 2024
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7. Start codon variant in LAG3 is associated with decreased LAG-3 expression and increased risk of autoimmune thyroid disease

Author: Saedis Saevarsdottir, Kristbjörg Bjarnadottir, Thorsteinn Markusson, Jonas Berglund, Thorunn A. Olafsdottir, Gisli H. Halldorsson, Gudrun Rutsdottir, Kristbjorg Gunnarsdottir, Asgeir Orn Arnthorsson, Sigrun H. Lund, Lilja Stefansdottir, Julius Gudmundsson, Ari J. Johannesson, Arni Sturluson, Asmundur Oddsson, Bjarni Halldorsson, Björn R. Ludviksson, Egil Ferkingstad, Erna V. Ivarsdottir, Gardar Sveinbjornsson, Gerdur Grondal, Gisli Masson, Grimur Hjorleifsson Eldjarn, Gudmundur A. Thorisson, Katla Kristjansdottir, Kirk U. Knowlton, Kristjan H. S. Moore, Sigurjon A. Gudjonsson, Solvi Rognvaldsson, Stacey Knight, Lincoln D. Nadauld, Hilma Holm, Olafur T. Magnusson, Patrick Sulem, Daniel F. Gudbjartsson, Thorunn Rafnar, Gudmar Thorleifsson, Pall Melsted, Gudmundur L. Norddahl, Ingileif Jonsdottir, and Kari Stefansson
Subjects: Science
Abstract: Abstract Autoimmune thyroid disease (AITD) is a common autoimmune disease. In a GWAS meta-analysis of 110,945 cases and 1,084,290 controls, 290 sequence variants at 225 loci are associated with AITD. Of these variants, 115 are previously unreported. Multiomics analysis yields 235 candidate genes outside the MHC-region and the findings highlight the importance of genes involved in T-cell regulation. A rare 5’-UTR variant (rs781745126-T, MAF = 0.13% in Iceland) in LAG3 has the largest effect (OR = 3.42, P = 2.2 × 10−16) and generates a novel start codon for an open reading frame upstream of the canonical protein translation initiation site. rs781745126-T reduces mRNA and surface expression of the inhibitory immune checkpoint LAG-3 co-receptor on activated lymphocyte subsets and halves LAG-3 levels in plasma among heterozygotes. All three homozygous carriers of rs781745126-T have AITD, of whom one also has two other T-cell mediated diseases, that is vitiligo and type 1 diabetes. rs781745126-T associates nominally with vitiligo (OR = 5.1, P = 6.5 × 10−3) but not with type 1 diabetes. Thus, the effect of rs781745126-T is akin to drugs that inhibit LAG-3, which unleash immune responses and can have thyroid dysfunction and vitiligo as adverse events. This illustrates how a multiomics approach can reveal potential drug targets and safety concerns.
Published: 2024
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8. GWAS meta-analysis reveals key risk loci in essential tremor pathogenesis

Author: Astros Th. Skuladottir, Lilja Stefansdottir, Gisli H. Halldorsson, Olafur A. Stefansson, Anna Bjornsdottir, Palmi Jonsson, Vala Palmadottir, Thorgeir E. Thorgeirsson, G. Bragi Walters, Rosa S. Gisladottir, Gyda Bjornsdottir, Gudrun A. Jonsdottir, Patrick Sulem, Daniel F. Gudbjartsson, Kirk U. Knowlton, David A. Jones, Aigar Ottas, Estonian Biobank, Ole B. Pedersen, Maria Didriksen, Søren Brunak, Karina Banasik, Thomas Folkmann Hansen, Christian Erikstrup, DBDS Genomic Consortium, Jan Haavik, Ole A. Andreassen, David Rye, Jannicke Igland, Sisse Rye Ostrowski, Lili A. Milani, Lincoln D. Nadauld, Hreinn Stefansson, and Kari Stefansson
Subjects: Biology (General), QH301-705.5
Abstract: Abstract Essential tremor (ET) is a prevalent neurological disorder with a largely unknown underlying biology. In this genome-wide association study meta-analysis, comprising 16,480 ET cases and 1,936,173 controls from seven datasets, we identify 12 sequence variants at 11 loci. Evaluating mRNA expression, splicing, plasma protein levels, and coding effects, we highlight seven putative causal genes at these loci, including CA3 and CPLX1. CA3 encodes Carbonic Anhydrase III and carbonic anhydrase inhibitors have been shown to decrease tremors. CPLX1, encoding Complexin-1, regulates neurotransmitter release. Through gene-set enrichment analysis, we identify a significant association with specific cell types, including dopaminergic and GABAergic neurons, as well as biological processes like Rho GTPase signaling. Genetic correlation analyses reveals a positive association between ET and Parkinson’s disease, depression, and anxiety-related phenotypes. This research uncovers risk loci, enhancing our knowledge of the complex genetics of this common but poorly understood disorder, and highlights CA3 and CPLX1 as potential therapeutic targets.
Published: 2024
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9. Gyrofluid simulations of turbulence and reconnection in space plasmas

Author: T. Passot, S.S. Cerri, C. Granier, D. Laveder, P.L. Sulem, and E. Tassi
Subjects: Collisionless plasmas, Alfvenic turbulence, Magnetic reconnection, Gyrofluids, Plasma physics. Ionized gases, QC717.6-718.8, Science
Abstract: A Hamiltonian two-field gyrofluid model is used to investigate the dynamics of an electron-ion collisionless plasma subject to a strong ambient magnetic field, within a spectral range extending from the magnetohydrodynamic (MHD) scales to the electron skin depth. This model isolates Alfvén, Kinetic Alfvén and Inertial Kinetic Alfvén waves that play a central role in space plasmas, and extends standard reduced fluid models to broader ranges of the plasma parameters. Recent numerical results are reviewed, including (i) the reconnection-mediated MHD turbulence developing from the collision of counter-propagating Alfvén wave packets, (ii) the specific features of the cascade dynamics in strongly imbalanced turbulence, including a possible link between the existence of a spectral transition range and the presence of co-propagating wave interactions at sub-ion scales, for which new simulations are reported, (iii) the influence of the ion-to-electron temperature ratio in two-dimensional collisionless magnetic reconnection. The role of electron finite Larmor radius corrections is pointed out and the extension of the present model to a four-field gyrofluid model is discussed. Such an extended model accurately describes electron finite Larmor radius effects at small or moderate values of the electron beta parameter, and also retains the coupling to slow magnetosonic waves.
Published: 2024
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10. X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements

Author: Markus Scholz, Katrin Horn, Janne Pott, Matthias Wuttke, Andreas Kühnapfel, M. Kamal Nasr, Holger Kirsten, Yong Li, Anselm Hoppmann, Mathias Gorski, Sahar Ghasemi, Man Li, Adrienne Tin, Jin-Fang Chai, Massimiliano Cocca, Judy Wang, Teresa Nutile, Masato Akiyama, Bjørn Olav Åsvold, Nisha Bansal, Mary L. Biggs, Thibaud Boutin, Hermann Brenner, Ben Brumpton, Ralph Burkhardt, Jianwen Cai, Archie Campbell, Harry Campbell, John Chalmers, Daniel I. Chasman, Miao Ling Chee, Miao Li Chee, Xu Chen, Ching-Yu Cheng, Renata Cifkova, Martha Daviglus, Graciela Delgado, Katalin Dittrich, Todd L. Edwards, Karlhans Endlich, J. Michael Gaziano, Ayush Giri, Franco Giulianini, Scott D. Gordon, Daniel F. Gudbjartsson, Stein Hallan, Pavel Hamet, Catharina A. Hartman, Caroline Hayward, Iris M. Heid, Jacklyn N. Hellwege, Bernd Holleczek, Hilma Holm, Nina Hutri-Kähönen, Kristian Hveem, Berend Isermann, Jost B. Jonas, Peter K. Joshi, Yoichiro Kamatani, Masahiro Kanai, Mika Kastarinen, Chiea Chuen Khor, Wieland Kiess, Marcus E. Kleber, Antje Körner, Peter Kovacs, Alena Krajcoviechova, Holly Kramer, Bernhard K. Krämer, Mikko Kuokkanen, Mika Kähönen, Leslie A. Lange, James P. Lash, Terho Lehtimäki, Hengtong Li, Bridget M. Lin, Jianjun Liu, Markus Loeffler, Leo-Pekka Lyytikäinen, Patrik K. E. Magnusson, Nicholas G. Martin, Koichi Matsuda, Yuri Milaneschi, Pashupati P. Mishra, Nina Mononen, Grant W. Montgomery, Dennis O. Mook-Kanamori, Josyf C. Mychaleckyj, Winfried März, Matthias Nauck, Kjell Nikus, Ilja M. Nolte, Raymond Noordam, Yukinori Okada, Isleifur Olafsson, Albertine J. Oldehinkel, Brenda W. J. H. Penninx, Markus Perola, Nicola Pirastu, Ozren Polasek, David J. Porteous, Tanja Poulain, Bruce M. Psaty, Ton J. Rabelink, Laura M. Raffield, Olli T. Raitakari, Humaira Rasheed, Dermot F. Reilly, Kenneth M. Rice, Anne Richmond, Paul M. Ridker, Jerome I. Rotter, Igor Rudan, Charumathi Sabanayagam, Veikko Salomaa, Neil Schneiderman, Ben Schöttker, Mario Sims, Harold Snieder, Klaus J. Stark, Kari Stefansson, Hannah Stocker, Michael Stumvoll, Patrick Sulem, Gardar Sveinbjornsson, Per O. Svensson, E-Shyong Tai, Kent D. Taylor, Bamidele O. Tayo, Andrej Teren, Yih-Chung Tham, Joachim Thiery, Chris H. L. Thio, Laurent F. Thomas, Johanne Tremblay, Anke Tönjes, Peter J. van der Most, Veronique Vitart, Uwe Völker, Ya Xing Wang, Chaolong Wang, Wen Bin Wei, John B. Whitfield, Sarah H. Wild, James F. Wilson, Thomas W. Winkler, Tien-Yin Wong, Mark Woodward, Xueling Sim, Audrey Y. Chu, Mary F. Feitosa, Unnur Thorsteinsdottir, Adriana M. Hung, Alexander Teumer, Nora Franceschini, Afshin Parsa, Anna Köttgen, Pascal Schlosser, and Cristian Pattaro
Subjects: Science
Abstract: Abstract X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.
Published: 2024
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11. An Empirical Study of Self-Supervised Learning with Wasserstein Distance

Author: Makoto Yamada, Yuki Takezawa, Guillaume Houry, Kira Michaela Düsterwald, Deborah Sulem, Han Zhao, and Yao-Hung Tsai
Subjects: optimal transport, Wasserstein distance, self-supervised learning, Science, Astrophysics, QB460-466, Physics, QC1-999
Abstract: In this study, we consider the problem of self-supervised learning (SSL) utilizing the 1-Wasserstein distance on a tree structure (a.k.a., Tree-Wasserstein distance (TWD)), where TWD is defined as the L1 distance between two tree-embedded vectors. In SSL methods, the cosine similarity is often utilized as an objective function; however, it has not been well studied when utilizing the Wasserstein distance. Training the Wasserstein distance is numerically challenging. Thus, this study empirically investigates a strategy for optimizing the SSL with the Wasserstein distance and finds a stable training procedure. More specifically, we evaluate the combination of two types of TWD (total variation and ClusterTree) and several probability models, including the softmax function, the ArcFace probability model, and simplicial embedding. We propose a simple yet effective Jeffrey divergence-based regularization method to stabilize optimization. Through empirical experiments on STL10, CIFAR10, CIFAR100, and SVHN, we find that a simple combination of the softmax function and TWD can obtain significantly lower results than the standard SimCLR. Moreover, a simple combination of TWD and SimSiam fails to train the model. We find that the model performance depends on the combination of TWD and probability model, and that the Jeffrey divergence regularization helps in model training. Finally, we show that the appropriate combination of the TWD and probability model outperforms cosine similarity-based representation learning.
Published: 2024
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12. Patented technologies in the extraction, preservation, and application of anthocyanins in food: A review

Author: Sulem Yali Granados-Balbuena, Vanesa Chicatto-Gasperín, Ericka Santacruz-Juárez, Erik Ocaranza-Sánchez, Carolina Ramírez-López, María Guadalupe García-Meza, Lilia Tapia-López, Raúl René Robles de la Torre, and María Reyna Robles López
Subjects: Anthocyanins, Patents, Application, Food, Natural colorants, Technology, Food processing and manufacture, TP368-456
Abstract: Color is an important parameter in food because it can be associated with quality. Since ancient times, natural dyes have been used in foods to make them attractive, but due to their poor stability to environmental factors and production processes, technologies emerged over time that led to getting artificial pigments with high stability, low production costs, and high dyeing capacity. However, some adverse indications of health damage have been reported, and that is why there is a growing interest in using natural colorants in food again. The red color is one of the most striking and important tones in the food sector since it is attractive, and it can produce expected taste sensations. One of the natural pigments that provide this red hue are anthocyanins, compounds that are widely distributed in plant sources, unlike artificial colors, have been associated with multiple health benefits. However, the application of anthocyanins represents a challenge due to their low stability against factors such as pH, oxygen, light, and temperature, so they are being stabilized through chemistry or physics way. This work aims to highlight the importance of anthocyanins and illustrate a summary of stabilization and conservation strategies used in patents applied in the food industry, as a methodological background to increase the use of natural pigments in diets.
Published: 2024
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13. Knowledge, attitude, and practice of dentists in the management of medical emergencies in India: A cross-sectional study

Author: Anabelle L.V.C. Fernandes, Jayraj B. Malik, Sulem R. Ansari, Sridhar Murali, and Jayapriya Thirupathii
Subjects: Attitude, Dentistry, Knowledge, Medical emergencies, Practice, Questionnaire, RK1-715
Abstract: Background: A medical emergency is an acute, unanticipated medical reaction or complication that threatens the patient's life or health and necessitates rapid attention or intervention. Since these emergencies can be life-threatening, the dentist's readiness is critical to avoid morbidity, mortality, and legal complications. Therefore, this study aims to assess dental students' and practitioners' knowledge, attitude, and practice in managing medical emergencies in India. Material and methods: A cross-sectional study was conducted at a private dental institute among 420 participants (318 males and 102 females) using a customized questionnaire consisting of sixteen questions - one open-ended and fifteen closed-ended. The data obtained was analysed using Chi-square test, Kruskal-Wallis H test, Mann –Whitney U test, and Spearman's rank correlation coefficient test. Results: Out of the 420 respondents, 416 (99.05 %) respondents believed that it is essential to obtain patients’ vital signs (blood pressure, pulse, respiratory rate, temperature) before starting any treatment. However, 345 (82.14 %) respondents had not taken any course in managing medical emergencies and only 196 (46.67 %) respondents were confident in handling a medical emergency. There was a statistically significant association (P
Published: 2023
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14. Sequence variant affects GCSAML splicing, mast cell specific proteins, and risk of urticaria

Author: Ragnar P. Kristjansson, Gudjon R. Oskarsson, Astros Skuladottir, Asmundur Oddsson, Solvi Rognvaldsson, Gardar Sveinbjornsson, Sigrun H. Lund, Brynjar O. Jensson, Edda L. Styrmisdottir, Gisli H. Halldorsson, Egil Ferkingstad, Grimur Hjorleifsson Eldjarn, Doruk Beyter, Snædis Kristmundsdottir, Kristinn Juliusson, Run Fridriksdottir, Gudny A. Arnadottir, Hildigunnur Katrinardottir, Margret H. Snorradottir, Vinicius Tragante, Lilja Stefansdottir, Erna V. Ivarsdottir, Gyda Bjornsdottir, Bjarni V. Halldorsson, Gudmar Thorleifsson, Bjorn R. Ludviksson, Pall T. Onundarson, Saedis Saevarsdottir, Pall Melsted, Gudmundur L. Norddahl, Unnur S. Bjornsdottir, Thorunn Olafsdottir, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Ingileif Jonsdottir, Patrick Sulem, and Kari Stefansson
Subjects: Biology (General), QH301-705.5
Abstract: Abstract Urticaria is a skin disorder characterized by outbreaks of raised pruritic wheals. In order to identify sequence variants associated with urticaria, we performed a meta-analysis of genome-wide association studies for urticaria with a total of 40,694 cases and 1,230,001 controls from Iceland, the UK, Finland, and Japan. We also performed transcriptome- and proteome-wide analyses in Iceland and the UK. We found nine sequence variants at nine loci associating with urticaria. The variants are at genes participating in type 2 immune responses and/or mast cell biology (CBLB, FCER1A, GCSAML, STAT6, TPSD1, ZFPM1), the innate immunity (C4), and NF-κB signaling. The most significant association was observed for the splice-donor variant rs56043070[A] (hg38: chr1:247556467) in GCSAML (MAF = 6.6%, OR = 1.24 (95%CI: 1.20–1.28), P-value = 3.6 × 10-44). We assessed the effects of the variants on transcripts, and levels of proteins relevant to urticaria pathophysiology. Our results emphasize the role of type 2 immune response and mast cell activation in the pathogenesis of urticaria. Our findings may point to an IgE-independent urticaria pathway that could help address unmet clinical need.
Published: 2023
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15. Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study

Author: Hilma Holm, Erna V. Ivarsdottir, Thorhildur Olafsdottir, Rosa Thorolfsdottir, Elias Eythorsson, Kristjan Norland, Rosa Gisladottir, Gudrun Jonsdottir, Unnur Unnsteinsdottir, Kristin E. Sveinsdottir, Benedikt A. Jonsson, Margret Andresdottir, David O. Arnar, Asgeir O. Arnthorsson, Kolbrún Birgisdottir, Kristbjorg Bjarnadottir, Solveig Bjarnadottir, Gyda Bjornsdottir, Gudmundur Einarsson, Berglind Eiriksdottir, Elisabet Eir Gardarsdottir, Thorarinn Gislason, Magnus Gottfredsson, Steinunn Gudmundsdottir, Julius Gudmundsson, Kristbjorg Gunnarsdottir, Anna Helgadottir, Dadi Helgason, Ingibjorg Hinriksdottir, Ragnar F. Ingvarsson, Sigga S. Jonasdottir, Ingileif Jonsdottir, Tekla H. Karlsdottir, Anna M. Kristinsdottir, Sigurdur Yngvi Kristinsson, Steinunn Kristjansdottir, Thorvardur J. Love, Dora Ludviksdottir, Gisli Masson, Gudmundur Norddahl, Thorunn Olafsdottir, Isleifur Olafsson, Thorunn Rafnar, Hrafnhildur L. Runolfsdottir, Jona Saemundsdottir, Svanur Sigurbjornsson, Kristin Sigurdardottir, Engilbert Sigurdsson, Martin I. Sigurdsson, Emil L. Sigurdsson, Valgerdur Steinthorsdottir, Gardar Sveinbjornsson, Emil A. Thorarensen, Bjarni Thorbjornsson, Brynja Thorsteinsdottir, Vinicius Tragante, Magnus O. Ulfarsson, Hreinn Stefansson, Thorsteinn Gislason, Mar Kristjansson, Runolfur Palsson, Patrick Sulem, Unnur Thorsteinsdottir, Gudmundur Thorgeirsson, Daniel F. Gudbjartsson, and Kari Stefansson
Subjects: Medicine
Abstract: Abstract Background Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. Methods We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5–18 months after infection. Results Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. Conclusions We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.
Published: 2023
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16. Frequency-specific contributions to auditory perceptual priors: Testing the predictive-coding hypothesis

Author: Itay Lieder, Aviel Sulem, and Merav Ahissar
Subjects: Biological sciences, Neuroscience, Sensory neuroscience, Science
Abstract: Summary: Perceptual priors formed by recent stimuli bias our immediate percept. These priors, expressing our implicit expectations, affect both high- and low-level processing stages. Yet, the nature of the inter-level interaction is unknown. Do priors operate top-down and bias low-level features toward recently experienced objects (predictive-coding hypothesis), or are low-level biases bottom-up driven and formed by local memory circuits? To decipher between these options in auditory perception, we used the “missing fundamental illusion”, enabling the dissociation of low-level components from the high-level pitch. Surprisingly, in contrast to predictive coding, when the fundamental frequency was missing, pitch contraction across timbre categories was not found to the previously perceived high-level pitch, but to the physically present frequency. This bottom-up contribution of low-level memory components to perceptual priors, operating independently of recent high-level percepts, may stabilize the perceptual organization and underlie continuity between similar low-level features belonging to different object categories in the auditory modality.
Published: 2024
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17. Sequence variants affecting the genome-wide rate of germline microsatellite mutations

Author: Snaedis Kristmundsdottir, Hakon Jonsson, Marteinn T. Hardarson, Gunnar Palsson, Doruk Beyter, Hannes P. Eggertsson, Arnaldur Gylfason, Gardar Sveinbjornsson, Guillaume Holley, Olafur A. Stefansson, Gisli H. Halldorsson, Sigurgeir Olafsson, Gudny. A. Arnadottir, Pall I. Olason, Ogmundur Eiriksson, Gisli Masson, Unnur Thorsteinsdottir, Thorunn Rafnar, Patrick Sulem, Agnar Helgason, Daniel F. Gudbjartsson, Bjarni V. Halldorsson, and Kari Stefansson
Subjects: Science
Abstract: Abstract Microsatellites are polymorphic tracts of short tandem repeats with one to six base-pair (bp) motifs and are some of the most polymorphic variants in the genome. Using 6084 Icelandic parent-offspring trios we estimate 63.7 (95% CI: 61.9–65.4) microsatellite de novo mutations (mDNMs) per offspring per generation, excluding one bp repeats motifs (homopolymers) the estimate is 48.2 mDNMs (95% CI: 46.7–49.6). Paternal mDNMs occur at longer repeats than maternal ones, which are in turn larger with a mean size of 3.4 bp vs 3.1 bp for paternal ones. mDNMs increase by 0.97 (95% CI: 0.90–1.04) and 0.31 (95% CI: 0.25–0.37) per year of father’s and mother’s age at conception, respectively. Here, we find two independent coding variants that associate with the number of mDNMs transmitted to offspring; The minor allele of a missense variant (allele frequency (AF) = 1.9%) in MSH2, a mismatch repair gene, increases transmitted mDNMs from both parents (effect: 13.1 paternal and 7.8 maternal mDNMs). A synonymous variant (AF = 20.3%) in NEIL2, a DNA damage repair gene, increases paternally transmitted mDNMs (effect: 4.4 mDNMs). Thus, the microsatellite mutation rate in humans is in part under genetic control.
Published: 2023
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18. Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality

Author: Asmundur Oddsson, Patrick Sulem, Gardar Sveinbjornsson, Gudny A. Arnadottir, Valgerdur Steinthorsdottir, Gisli H. Halldorsson, Bjarni A. Atlason, Gudjon R. Oskarsson, Hannes Helgason, Henriette Svarre Nielsen, David Westergaard, Juha M. Karjalainen, Hildigunnur Katrinardottir, Run Fridriksdottir, Brynjar O. Jensson, Vinicius Tragante, Egil Ferkingstad, Hakon Jonsson, Sigurjon A. Gudjonsson, Doruk Beyter, Kristjan H. S. Moore, Helga B. Thordardottir, Snaedis Kristmundsdottir, Olafur A. Stefansson, Solbritt Rantapää-Dahlqvist, Ida Elken Sonderby, Maria Didriksen, Pernilla Stridh, Jan Haavik, Laufey Tryggvadottir, Oleksandr Frei, G. Bragi Walters, Ingrid Kockum, Henrik Hjalgrim, Thorunn A. Olafsdottir, Geir Selbaek, Mette Nyegaard, Christian Erikstrup, Thorsten Brodersen, Saedis Saevarsdottir, Tomas Olsson, Kaspar Rene Nielsen, Asgeir Haraldsson, Mie Topholm Bruun, Thomas Folkmann Hansen, DBDS Genomic Consortium, Thora Steingrimsdottir, Rikke Louise Jacobsen, Rolv T. Lie, Srdjan Djurovic, Lars Alfredsson, Aitzkoa Lopez de Lapuente Portilla, Soren Brunak, Pall Melsted, Bjarni V. Halldorsson, Jona Saemundsdottir, Olafur Th. Magnusson, Leonid Padyukov, Karina Banasik, Thorunn Rafnar, Johan Askling, Lars Klareskog, Ole Birger Pedersen, Gisli Masson, Alexandra Havdahl, Bjorn Nilsson, Ole A. Andreassen, Mark Daly, Sisse Rye Ostrowski, Ingileif Jonsdottir, Hreinn Stefansson, Hilma Holm, Agnar Helgason, Unnur Thorsteinsdottir, Kari Stefansson, and Daniel F. Gudbjartsson
Subjects: Science
Abstract: Abstract Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
Published: 2023
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19. Factor B Mutation in Monozygotic Twins Discordant for Atypical Hemolytic Uremic Syndrome

Author: Sigridur Sunna Aradottir, Ann-Charlotte Kristoffersson, Brynjar O. Jensson, Patrick Sulem, Henning Gong, Runolfur Palsson, and Diana Karpman
Subjects: atypical hemolytic uremic syndrome, complement, Factor B, genetics, monozygotic twins, Diseases of the genitourinary system. Urology, RC870-923
Published: 2023
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20. Bioprocess of Gibberellic Acid by Fusarium fujikuroi: The Challenge of Regulation, Raw Materials, and Product Yields

Author: Aranza Hernández Rodríguez, Adrián Díaz Pacheco, Shirlley Elizabeth Martínez Tolibia, Yazmin Melendez Xicohtencatl, Sulem Yali Granados Balbuena, and Víctor Eric López y López
Subjects: plant growth regulator, bakanae, fermentative processes, production yields, gibberellins market, Biology (General), QH301-705.5
Abstract: Gibberellic acid (GA3) is a tetracyclic diterpenoid carboxylic acid synthesized by the secondary metabolism of Fusarium fujikuroi. This phytohormone is widely studied due to the advantages it offers as a plant growth regulator, such as growth stimulation, senescence delay, flowering induction, increased fruit size, and defense against abiotic or biotic stress, which improve the quality and yield of crops. Therefore, GA3 has been considered as an innovative strategy to improve agricultural production. However, the yields obtained at large scale are insufficient for the current market demand. This low productivity is attributed to the lack of adequate parameters to optimize the fermentation process, as well as the complexity of its regulation. Therefore, this article describes the latest advances for potentializing the GA3 production process, including an analysis of its origins from crops, the benefits of its application, the related biosynthetic metabolism, the maximum yields achieved from production processes, and their association with genetic engineering techniques for GA3 producers. This work provides a new perspective on the critical points of the production process, in order to overcome the limits surrounding this modern line of bioengineering.
Published: 2024
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21. Screening for Rare Coding Variants That Associate With the QTc Interval in Iceland

Author: Gardar Sveinbjornsson, Bara D. Benediktsdottir, Gunnlaugur Sigfusson, Kristjan Norland, Olafur B. Davidsson, Rosa B. Thorolfsdottir, Vinicius Tragante, Gudny A. Arnadottir, Brynjar O. Jensson, Hildigunnur Katrinardottir, Run Fridriksdottir, Hallbera Gudmundsdottir, Hildur M. Aegisdottir, Brynjar Fridriksson, Gudmundur Thorgeirsson, Vidar Magnusson, Asmundur Oddsson, Patrick Sulem, Daniel F. Gudbjartsson, Hilma Holm, David O. Arnar, and Kari Stefansson
Subjects: genetic epidemiology, genetics, long‐QT syndrome, precision medicine, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Long‐QT syndrome (LQTS) is a cardiac repolarization abnormality that can lead to sudden cardiac death. The most common causes are rare coding variants in the genes KCNQ1, KCNH2, and SCN5A. The data on LQTS epidemiology are limited, and information on expressivity and penetrance of pathogenic variants is sparse. Methods and Results We screened for rare coding variants associated with the corrected QT (QTc) interval in Iceland. We explored the frequency of the identified variants, their penetrance, and their association with severe events. Twelve variants were associated with the QTc interval. Five in KCNQ1, 3 in KCNH2, 2 in cardiomyopathy genes MYBPC3 and PKP2, and 2 in genes where coding variants have not been associated with the QTc interval, ISOC1 and MYOM2. The combined carrier frequency of the 8 variants in the previously known LQTS genes was 530 per 100 000 individuals (1:190). p.Tyr315Cys and p.Leu273Phe in KCNQ1 were associated with having a mean QTc interval longer than 500 ms (P=4.2×10−7; odds ratio [OR], 38.6; P=8.4×10−10, OR, 26.5; respectively), and p.Leu273Phe was associated with sudden cardiac death (P=0.0034; OR, 2.99). p.Val215Met in KCNQ1 was carried by 1 in 280 Icelanders, had a smaller effect on the QTc interval (P=1.8×10−44; effect, 22.8 ms), and did not associate with severe clinical events. Conclusions The carrier frequency of associating variants in LQTS genes was higher than previous estimates of the prevalence of LQTS. The variants have variable effects on the QTc interval, and carriers of p.Tyr315Cys and p.Leu273Phe have a more severe disease than carriers of p.Val215Met. These data could lead to improved identification, risk stratification, and a more precise clinical approach to those with QTc prolongation.
Published: 2023
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22. HLA alleles, disease severity, and age associate with T-cell responses following infection with SARS-CoV-2

Author: Thorunn A. Olafsdottir, Kristbjorg Bjarnadottir, Gudmundur L. Norddahl, Gisli H. Halldorsson, Pall Melsted, Kristbjorg Gunnarsdottir, Erna Ivarsdottir, Thorhildur Olafsdottir, Asgeir O. Arnthorsson, Fannar Theodors, Elias Eythorsson, Dadi Helgason, Hannes P. Eggertsson, Gisli Masson, Sólveig Bjarnadottir, Saedis Saevarsdottir, Hrafnhildur L. Runolfsdottir, Isleifur Olafsson, Jona Saemundsdottir, Martin I. Sigurdsson, Ragnar F. Ingvarsson, Runolfur Palsson, Gudmundur Thorgeirsson, Bjarni V. Halldorsson, Hilma Holm, Mar Kristjansson, Patrick Sulem, Unnur Thorsteinsdottir, Ingileif Jonsdottir, Daniel F. Gudbjartsson, and Kari Stefansson
Subjects: Biology (General), QH301-705.5
Abstract: A study of 768 convalescent SARS CoV-2-infected and 500 uninfected Icelanders reveals broad and stable T-cell responses 3-8 months from infection. HLA alleles, disease severity, and age contribute to the heterogeneity of cellular immunity.
Published: 2022
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23. Effect of booster vaccination against Delta and Omicron SARS-CoV-2 variants in Iceland

Author: Gudmundur L. Norddahl, Pall Melsted, Kristbjorg Gunnarsdottir, Gisli H. Halldorsson, Thorunn A. Olafsdottir, Arnaldur Gylfason, Mar Kristjansson, Olafur T. Magnusson, Patrick Sulem, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Ingileif Jonsdottir, and Kari Stefansson
Subjects: Science
Abstract: Iceland has used four different SARS-CoV-2 vaccines in various combinations. Here, the authors describe differences in the immune responses elicited by different initial/booster vaccine combinations, and then use population-level data to assess the effects of booster doses against Delta and Omicron infection.
Published: 2022
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24. Genetic architecture of band neutrophil fraction in Iceland

Author: Gudjon R. Oskarsson, Magnus K. Magnusson, Asmundur Oddsson, Brynjar O. Jensson, Run Fridriksdottir, Gudny A. Arnadottir, Hildigunnur Katrinardottir, Solvi Rognvaldsson, Gisli H. Halldorsson, Gardar Sveinbjornsson, Erna V. Ivarsdottir, Lilja Stefansdottir, Egil Ferkingstad, Kristjan Norland, Vinicius Tragante, Jona Saemundsdottir, Aslaug Jonasdottir, Adalbjorg Jonasdottir, Svanhvit Sigurjonsdottir, Karen O. Petursdottir, Olafur B. Davidsson, Thorunn Rafnar, Hilma Holm, Isleifur Olafsson, Pall T. Onundarson, Brynjar Vidarsson, Olof Sigurdardottir, Gisli Masson, Daniel F. Gudbjartsson, Ingileif Jonsdottir, Gudmundur L. Norddahl, Unnur Thorsteinsdottir, Patrick Sulem, and Kari Stefansson
Subjects: Biology (General), QH301-705.5
Abstract: A GWAS in Iceland reveals that variants in inner nuclear membrane proteins are associated with nuclear morphology of granulocytes and band neutrophil fraction.
Published: 2022
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25. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Author: Thomas W. Winkler, Humaira Rasheed, Alexander Teumer, Mathias Gorski, Bryce X. Rowan, Kira J. Stanzick, Laurent F. Thomas, Adrienne Tin, Anselm Hoppmann, Audrey Y. Chu, Bamidele Tayo, Chris H. L. Thio, Daniele Cusi, Jin-Fang Chai, Karsten B. Sieber, Katrin Horn, Man Li, Markus Scholz, Massimiliano Cocca, Matthias Wuttke, Peter J. van der Most, Qiong Yang, Sahar Ghasemi, Teresa Nutile, Yong Li, Giulia Pontali, Felix Günther, Abbas Dehghan, Adolfo Correa, Afshin Parsa, Agnese Feresin, Aiko P. J. de Vries, Alan B. Zonderman, Albert V. Smith, Albertine J. Oldehinkel, Alessandro De Grandi, Alexander R. Rosenkranz, Andre Franke, Andrej Teren, Andres Metspalu, Andrew A. Hicks, Andrew P. Morris, Anke Tönjes, Anna Morgan, Anna I. Podgornaia, Annette Peters, Antje Körner, Anubha Mahajan, Archie Campbell, Barry I. Freedman, Beatrice Spedicati, Belen Ponte, Ben Schöttker, Ben Brumpton, Bernhard Banas, Bernhard K. Krämer, Bettina Jung, Bjørn Olav Åsvold, Blair H. Smith, Boting Ning, Brenda W. J. H. Penninx, Brett R. Vanderwerff, Bruce M. Psaty, Candace M. Kammerer, Carl D. Langefeld, Caroline Hayward, Cassandra N. Spracklen, Cassianne Robinson-Cohen, Catharina A. Hartman, Cecilia M. Lindgren, Chaolong Wang, Charumathi Sabanayagam, Chew-Kiat Heng, Chiara Lanzani, Chiea-Chuen Khor, Ching-Yu Cheng, Christian Fuchsberger, Christian Gieger, Christian M. Shaffer, Christina-Alexandra Schulz, Cristen J. Willer, Daniel I. Chasman, Daniel F. Gudbjartsson, Daniela Ruggiero, Daniela Toniolo, Darina Czamara, David J. Porteous, Dawn M. Waterworth, Deborah Mascalzoni, Dennis O. Mook-Kanamori, Dermot F. Reilly, E. Warwick Daw, Edith Hofer, Eric Boerwinkle, Erika Salvi, Erwin P. Bottinger, E-Shyong Tai, Eulalia Catamo, Federica Rizzi, Feng Guo, Fernando Rivadeneira, Franco Guilianini, Gardar Sveinbjornsson, Georg Ehret, Gerard Waeber, Ginevra Biino, Giorgia Girotto, Giorgio Pistis, Girish N. Nadkarni, Graciela E. Delgado, Grant W. Montgomery, Harold Snieder, Harry Campbell, Harvey D. White, He Gao, Heather M. Stringham, Helena Schmidt, Hengtong Li, Hermann Brenner, Hilma Holm, Holgen Kirsten, Holly Kramer, Igor Rudan, Ilja M. Nolte, Ioanna Tzoulaki, Isleifur Olafsson, Jade Martins, James P. Cook, James F. Wilson, Jan Halbritter, Janine F. Felix, Jasmin Divers, Jaspal S. Kooner, Jeannette Jen-Mai Lee, Jeffrey O’Connell, Jerome I. Rotter, Jianjun Liu, Jie Xu, Joachim Thiery, Johan Ärnlöv, Johanna Kuusisto, Johanna Jakobsdottir, Johanne Tremblay, John C. Chambers, John B. Whitfield, John M. Gaziano, Jonathan Marten, Josef Coresh, Jost B. Jonas, Josyf C. Mychaleckyj, Kaare Christensen, Kai-Uwe Eckardt, Karen L. Mohlke, Karlhans Endlich, Katalin Dittrich, Kathleen A. Ryan, Kenneth M. Rice, Kent D. Taylor, Kevin Ho, Kjell Nikus, Koichi Matsuda, Konstantin Strauch, Kozeta Miliku, Kristian Hveem, Lars Lind, Lars Wallentin, Laura M. Yerges-Armstrong, Laura M. Raffield, Lawrence S. Phillips, Lenore J. Launer, Leo-Pekka Lyytikäinen, Leslie A. Lange, Lorena Citterio, Lucija Klaric, M. Arfan Ikram, Marcus Ising, Marcus E. Kleber, Margherita Francescatto, Maria Pina Concas, Marina Ciullo, Mario Piratsu, Marju Orho-Melander, Markku Laakso, Markus Loeffler, Markus Perola, Martin H. de Borst, Martin Gögele, Martina La Bianca, Mary Ann Lukas, Mary F. Feitosa, Mary L. Biggs, Mary K. Wojczynski, Maryam Kavousi, Masahiro Kanai, Masato Akiyama, Masayuki Yasuda, Matthias Nauck, Melanie Waldenberger, Miao-Li Chee, Miao-Ling Chee, Michael Boehnke, Michael H. Preuss, Michael Stumvoll, Michael A. Province, Michele K. Evans, Michelle L. O’Donoghue, Michiaki Kubo, Mika Kähönen, Mika Kastarinen, Mike A. Nalls, Mikko Kuokkanen, Mohsen Ghanbari, Murielle Bochud, Navya Shilpa Josyula, Nicholas G. Martin, Nicholas Y. Q. Tan, Nicholette D. Palmer, Nicola Pirastu, Nicole Schupf, Niek Verweij, Nina Hutri-Kähönen, Nina Mononen, Nisha Bansal, Olivier Devuyst, Olle Melander, Olli T. Raitakari, Ozren Polasek, Paolo Manunta, Paolo Gasparini, Pashupati P. Mishra, Patrick Sulem, Patrik K. E. Magnusson, Paul Elliott, Paul M. Ridker, Pavel Hamet, Per O. Svensson, Peter K. Joshi, Peter Kovacs, Peter P. Pramstaller, Peter Rossing, Peter Vollenweider, Pim van der Harst, Rajkumar Dorajoo, Ralene Z. H. Sim, Ralph Burkhardt, Ran Tao, Raymond Noordam, Reedik Mägi, Reinhold Schmidt, Renée de Mutsert, Rico Rueedi, Rob M. van Dam, Robert J. Carroll, Ron T. Gansevoort, Ruth J. F. Loos, Sala Cinzia Felicita, Sanaz Sedaghat, Sandosh Padmanabhan, Sandra Freitag-Wolf, Sarah A. Pendergrass, Sarah E. Graham, Scott D. Gordon, Shih-Jen Hwang, Shona M. Kerr, Simona Vaccargiu, Snehal B. Patil, Stein Hallan, Stephan J. L. Bakker, Su-Chi Lim, Susanne Lucae, Suzanne Vogelezang, Sven Bergmann, Tanguy Corre, Tarunveer S. Ahluwalia, Terho Lehtimäki, Thibaud S. Boutin, Thomas Meitinger, Tien-Yin Wong, Tobias Bergler, Ton J. Rabelink, Tõnu Esko, Toomas Haller, Unnur Thorsteinsdottir, Uwe Völker, Valencia Hui Xian Foo, Veikko Salomaa, Veronique Vitart, Vilmantas Giedraitis, Vilmundur Gudnason, Vincent W. V. Jaddoe, Wei Huang, Weihua Zhang, Wen Bin Wei, Wieland Kiess, Winfried März, Wolfgang Koenig, Wolfgang Lieb, Xin Gao, Xueling Sim, Ya Xing Wang, Yechiel Friedlander, Yih-Chung Tham, Yoichiro Kamatani, Yukinori Okada, Yuri Milaneschi, Zhi Yu, Lifelines cohort study, DiscovEHR/MyCode study, VA Million Veteran Program, Klaus J. Stark, Kari Stefansson, Carsten A. Böger, Adriana M. Hung, Florian Kronenberg, Anna Köttgen, Cristian Pattaro, and Iris M. Heid
Subjects: Biology (General), QH301-705.5
Abstract: A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.
Published: 2022
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26. A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome

Author: Astros Th. Skuladottir, Gyda Bjornsdottir, Egil Ferkingstad, Gudmundur Einarsson, Lilja Stefansdottir, Muhammad Sulaman Nawaz, Asmundur Oddsson, Thorunn A. Olafsdottir, Saedis Saevarsdottir, G. Bragi Walters, Sigurdur H. Magnusson, Anna Bjornsdottir, Olafur A. Sveinsson, Arnor Vikingsson, Thomas Folkmann Hansen, Rikke Louise Jacobsen, Christian Erikstrup, Michael Schwinn, Søren Brunak, Karina Banasik, Sisse Rye Ostrowski, Anders Troelsen, Cecilie Henkel, Ole Birger Pedersen, DBDS Genetic Consortium, Ingileif Jonsdottir, Daniel F. Gudbjartsson, Patrick Sulem, Thorgeir E. Thorgeirsson, Hreinn Stefansson, and Kari Stefansson
Subjects: Science
Abstract: The underlying genetics of carpal tunnel syndrome is not well understood. Here, the authors perform a GWAS meta-analysis for carpal tunnel syndrome finding variants at 50 loci with connections to the extracellular matrix discovered through various functional analyses.
Published: 2022
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27. Population-level deficit of homozygosity unveils CPSF3 as an intellectual disability syndrome gene

Author: Gudny A. Arnadottir, Asmundur Oddsson, Brynjar O. Jensson, Svanborg Gisladottir, Mariella T. Simon, Asgeir O. Arnthorsson, Hildigunnur Katrinardottir, Run Fridriksdottir, Erna V. Ivarsdottir, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Rebekah Barrick, Jona Saemundsdottir, Louise le Roux, Gudjon R. Oskarsson, Jurate Asmundsson, Thora Steffensen, Kjartan R. Gudmundsson, Petur Ludvigsson, Jon J. Jonsson, Gisli Masson, Ingileif Jonsdottir, Hilma Holm, Jon G. Jonasson, Olafur Th. Magnusson, Olafur Thorarensen, Jose Abdenur, Gudmundur L. Norddahl, Daniel F. Gudbjartsson, Hans T. Bjornsson, Unnur Thorsteinsdottir, Patrick Sulem, and Kari Stefansson
Subjects: Science
Abstract: While the consequences of homozygous loss of function variants have been studied, the effect of missense variants is less understood. Here, the authors identify pathogenic genotypes through an observed deficit of homozygous carriers of missense variants in a population, elucidating previously unexplained recessive disease and miscarriage.
Published: 2022
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28. Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology

Author: Gyda Bjornsdottir, Lilja Stefansdottir, Gudmar Thorleifsson, Patrick Sulem, Kristjan Norland, Egil Ferkingstad, Asmundur Oddsson, Florian Zink, Sigrun H. Lund, Muhammad S. Nawaz, G. Bragi Walters, Astros Th. Skuladottir, Sigurjon A. Gudjonsson, Gudmundur Einarsson, Gisli H. Halldorsson, Valgerdur Bjarnadottir, Gardar Sveinbjornsson, Anna Helgadottir, Unnur Styrkarsdottir, Larus J. Gudmundsson, Ole B. Pedersen, Thomas Folkmann Hansen, Thomas Werge, Karina Banasik, Anders Troelsen, Soren T. Skou, Lise Wegner Thørner, Christian Erikstrup, Kaspar Rene Nielsen, Susan Mikkelsen, DBDS Genetic Consortium, GO Consortium, Ingileif Jonsdottir, Aron Bjornsson, Ingvar H. Olafsson, Elfar Ulfarsson, Josep Blondal, Arnor Vikingsson, Soren Brunak, Sisse R. Ostrowski, Henrik Ullum, Unnur Thorsteinsdottir, Hreinn Stefansson, Daniel F. Gudbjartsson, Thorgeir E. Thorgeirsson, and Kari Stefansson
Subjects: Science
Abstract: Little is known about the biology of back pain, a leading cause of disability. Here the authors report 30 new back pain loci, implicating genes involved in cartilage/bone biology, as well as neurological and inflammatory processes.
Published: 2022
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29. A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo

Author: Astros Th. Skuladottir, Gyda Bjornsdottir, Muhammad Sulaman Nawaz, Hannes Petersen, Solvi Rognvaldsson, Kristjan Helgi Swerford Moore, Pall I. Olafsson, Sigurður H. Magnusson, Anna Bjornsdottir, Olafur A. Sveinsson, Gudrun R. Sigurdardottir, Saedis Saevarsdottir, Erna V. Ivarsdottir, Lilja Stefansdottir, Bjarni Gunnarsson, Joseph B. Muhlestein, Kirk U. Knowlton, David A. Jones, Lincoln D. Nadauld, Annette M. Hartmann, Dan Rujescu, Michael Strupp, G. Bragi Walters, Thorgeir E. Thorgeirsson, Ingileif Jonsdottir, Hilma Holm, Gudmar Thorleifsson, Daniel F. Gudbjartsson, Patrick Sulem, Hreinn Stefansson, and Kari Stefansson
Subjects: Biology (General), QH301-705.5
Abstract: Astros Skuladottir et al. conducted a genome-wide association study on 48,072 vertigo cases and 894,541 controls from four populations with European ancestries. They identified six common variants associated with vertigo, thereby providing further insight into the etiology of vestibular disorders.
Published: 2021
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30. Author Correction: Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology

Author: Gyda Bjornsdottir, Lilja Stefansdottir, Gudmar Thorleifsson, Patrick Sulem, Kristjan Norland, Egil Ferkingstad, Asmundur Oddsson, Florian Zink, Sigrun H. Lund, Muhammad S. Nawaz, G. Bragi Walters, Astros Th. Skuladottir, Sigurjon A. Gudjonsson, Gudmundur Einarsson, Gisli H. Halldorsson, Valgerdur Bjarnadottir, Gardar Sveinbjornsson, Anna Helgadottir, Unnur Styrkarsdottir, Larus J. Gudmundsson, Ole B. Pedersen, Thomas Folkmann Hansen, Thomas Werge, Karina Banasik, Anders Troelsen, Soren T. Skou, Lise Wegner Thørner, Christian Erikstrup, Kaspar Rene Nielsen, Susan Mikkelsen, DBDS Genetic Consortium, GO Consortium, Ingileif Jonsdottir, Aron Bjornsson, Ingvar H. Olafsson, Elfar Ulfarsson, Josep Blondal, Arnor Vikingsson, Soren Brunak, Sisse R. Ostrowski, Henrik Ullum, Unnur Thorsteinsdottir, Hreinn Stefansson, Daniel F. Gudbjartsson, Thorgeir E. Thorgeirsson, and Kari Stefansson
Subjects: Science
Published: 2022
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31. Publisher Correction: Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality

Author: Asmundur Oddsson, Patrick Sulem, Gardar Sveinbjornsson, Gudny A. Arnadottir, Valgerdur Steinthorsdottir, Gisli H. Halldorsson, Bjarni A. Atlason, Gudjon R. Oskarsson, Hannes Helgason, Henriette Svarre Nielsen, David Westergaard, Juha M. Karjalainen, Hildigunnur Katrinardottir, Run Fridriksdottir, Brynjar O. Jensson, Vinicius Tragante, Egil Ferkingstad, Hakon Jonsson, Sigurjon A. Gudjonsson, Doruk Beyter, Kristjan H. S. Moore, Helga B. Thordardottir, Snaedis Kristmundsdottir, Olafur A. Stefansson, Solbritt Rantapää-Dahlqvist, Ida Elken Sonderby, Maria Didriksen, Pernilla Stridh, Jan Haavik, Laufey Tryggvadottir, Oleksandr Frei, G. Bragi Walters, Ingrid Kockum, Henrik Hjalgrim, Thorunn A. Olafsdottir, Geir Selbaek, Mette Nyegaard, Christian Erikstrup, Thorsten Brodersen, Saedis Saevarsdottir, Tomas Olsson, Kaspar Rene Nielsen, Asgeir Haraldsson, Mie Topholm Bruun, Thomas Folkmann Hansen, DBDS Genomic Consortium, Thora Steingrimsdottir, Rikke Louise Jacobsen, Rolv T. Lie, Srdjan Djurovic, Lars Alfredsson, Aitzkoa Lopez de Lapuente Portilla, Soren Brunak, Pall Melsted, Bjarni V. Halldorsson, Jona Saemundsdottir, Olafur Th. Magnusson, Leonid Padyukov, Karina Banasik, Thorunn Rafnar, Johan Askling, Lars Klareskog, Ole Birger Pedersen, Gisli Masson, Alexandra Havdahl, Bjorn Nilsson, Ole A. Andreassen, Mark Daly, Sisse Rye Ostrowski, Ingileif Jonsdottir, Hreinn Stefansson, Hilma Holm, Agnar Helgason, Unnur Thorsteinsdottir, Kari Stefansson, and Daniel F. Gudbjartsson
Subjects: Science
Published: 2023
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32. Predicting the probability of death using proteomics

Author: Thjodbjorg Eiriksdottir, Steinthor Ardal, Benedikt A. Jonsson, Sigrun H. Lund, Erna V. Ivarsdottir, Kristjan Norland, Egil Ferkingstad, Hreinn Stefansson, Ingileif Jonsdottir, Hilma Holm, Thorunn Rafnar, Jona Saemundsdottir, Gudmundur L. Norddahl, Gudmundur Thorgeirsson, Daniel F. Gudbjartsson, Patrick Sulem, Unnur Thorsteinsdottir, Kari Stefansson, and Magnus O. Ulfarsson
Subjects: Biology (General), QH301-705.5
Abstract: Eiriksdottir et al. use a temporal proteomic dataset from over 22,000 Icelandic individuals to identify predictors and predict all-cause mortality. Their findings suggest that the plasma proteome may be of value in general health screening for risk of death.
Published: 2021
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33. Molecular benchmarks of a SARS-CoV-2 epidemic

Author: Hakon Jonsson, Olafur T. Magnusson, Pall Melsted, Jonas Berglund, Arna B. Agustsdottir, Berglind Eiríksdottir, Run Fridriksdottir, Elisabet Eir Garðarsdottir, Gudmundur Georgsson, Olafia S. Gretarsdottir, Kjartan R. Guðmundsson, Thora Rosa Gunnarsdottir, Hannes Eggertsson, Arnaldur Gylfason, Hilma Holm, Brynjar O. Jensson, Aslaug Jonasdottir, Frosti Jonsson, Kamilla S. Josefsdottir, Marianna Thordardottir, Karl G. Kristinsson, Þórður Kristjánsson, Droplaug N. Magnusdottir, Louise le Roux, Jona Saemundsdottir, Asgeir Sigurdsson, Gudrun Sigmundsdottir, Gardar Sveinbjornsson, Solvi Rognvaldsson, Ogmundur Eiriksson, Magnus Karl Magnusson, Kristin Eva Sveinsdottir, Maney Sveinsdottir, Emil Aron Thorarensen, Bjarni Thorbjornsson, Arthur Löve, Gudmundur L. Norddahl, Ingileif Jonsdottir, Patrick Sulem, Gisli Masson, Alma Moller, Thorolfur Gudnason, Mar Kristjansson, Agnar Helgason, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, and Kari Stefansson
Subjects: Science
Abstract: The concentration of SARS-CoV-2 changes during an individual’s infection, and mutations accumulate as viruses are transmitted between people. Here, the authors use data from Iceland to demonstrate how this information can be exploited at the population-level to determine the phase of the epidemic.
Published: 2021
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34. The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis

Author: Erna V. Ivarsdottir, Hilma Holm, Stefania Benonisdottir, Thorhildur Olafsdottir, Gardar Sveinbjornsson, Gudmar Thorleifsson, Hannes P. Eggertsson, Gisli H. Halldorsson, Kristjan E. Hjorleifsson, Pall Melsted, Arnaldur Gylfason, Gudny A. Arnadottir, Asmundur Oddsson, Brynjar O. Jensson, Aslaug Jonasdottir, Adalbjorg Jonasdottir, Thorhildur Juliusdottir, Lilja Stefansdottir, Vinicius Tragante, Bjarni V. Halldorsson, Hannes Petersen, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Patrick Sulem, Ingibjorg Hinriksdottir, Ingileif Jonsdottir, Daniel F. Gudbjartsson, and Kari Stefansson
Subjects: Biology (General), QH301-705.5
Abstract: Erna Ivarsdottir et al. report a genome-wide association meta-analysis for age-related hearing loss in the Icelandic and UK populations. They identify 21 novel variants, 13 of which are rare, and reveal a genetic correlation between age-related hearing loss and tinnitus.
Published: 2021
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35. A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis

Author: Steven Bell, Andreas S. Rigas, Magnus K. Magnusson, Egil Ferkingstad, Elias Allara, Gyda Bjornsdottir, Anna Ramond, Erik Sørensen, Gisli H. Halldorsson, Dirk S. Paul, Kristoffer S. Burgdorf, Hannes P. Eggertsson, Joanna M. M. Howson, Lise W. Thørner, Snaedis Kristmundsdottir, William J. Astle, Christian Erikstrup, Jon K. Sigurdsson, Dragana Vuckovic, Khoa M. Dinh, Vinicius Tragante, Praveen Surendran, Ole B. Pedersen, Brynjar Vidarsson, Tao Jiang, Helene M. Paarup, Pall T. Onundarson, Parsa Akbari, Kaspar R. Nielsen, Sigrun H. Lund, Kristinn Juliusson, Magnus I. Magnusson, Michael L. Frigge, Asmundur Oddsson, Isleifur Olafsson, Stephen Kaptoge, Henrik Hjalgrim, Gudmundur Runarsson, Angela M. Wood, Ingileif Jonsdottir, Thomas F. Hansen, Olof Sigurdardottir, Hreinn Stefansson, David Rye, DBDS Genomic Consortium, James E. Peters, David Westergaard, Hilma Holm, Nicole Soranzo, Karina Banasik, Gudmar Thorleifsson, Willem H. Ouwehand, Unnur Thorsteinsdottir, David J. Roberts, Patrick Sulem, Adam S. Butterworth, Daniel F. Gudbjartsson, John Danesh, Søren Brunak, Emanuele Di Angelantonio, Henrik Ullum, and Kari Stefansson
Subjects: Biology (General), QH301-705.5
Abstract: Bell et al. report 46 new loci associated with biomarkers of iron homeostasis, including ferritin levels, iron binding capacity, and iron saturation, in the Icelandic, Danish and UK populations. The associated loci point to new iron-regulating proteins and important genetic differences between men and women.
Published: 2021
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36. PopDel identifies medium-size deletions simultaneously in tens of thousands of genomes

Author: Sebastian Niehus, Hákon Jónsson, Janina Schönberger, Eythór Björnsson, Doruk Beyter, Hannes P. Eggertsson, Patrick Sulem, Kári Stefánsson, Bjarni V. Halldórsson, and Birte Kehr
Subjects: Science
Abstract: Identifying structural variants (SVs) from whole genome sequence data has been a significant bioinformatic challenge. Here, the authors describe PopDel, which uses a joint SV detection approach to reliably and efficiently identify 500-10,000 bp deletions across large population cohorts.
Published: 2021
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37. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ioanna Ntalla, Lu-Chen Weng, James H. Cartwright, Amelia Weber Hall, Gardar Sveinbjornsson, Nathan R. Tucker, Seung Hoan Choi, Mark D. Chaffin, Carolina Roselli, Michael R. Barnes, Borbala Mifsud, Helen R. Warren, Caroline Hayward, Jonathan Marten, James J. Cranley, Maria Pina Concas, Paolo Gasparini, Thibaud Boutin, Ivana Kolcic, Ozren Polasek, Igor Rudan, Nathalia M. Araujo, Maria Fernanda Lima-Costa, Antonio Luiz P. Ribeiro, Renan P. Souza, Eduardo Tarazona-Santos, Vilmantas Giedraitis, Erik Ingelsson, Anubha Mahajan, Andrew P. Morris, Fabiola Del Greco M, Luisa Foco, Martin Gögele, Andrew A. Hicks, James P. Cook, Lars Lind, Cecilia M. Lindgren, Johan Sundström, Christopher P. Nelson, Muhammad B. Riaz, Nilesh J. Samani, Gianfranco Sinagra, Sheila Ulivi, Mika Kähönen, Pashupati P. Mishra, Nina Mononen, Kjell Nikus, Mark J. Caulfield, Anna Dominiczak, Sandosh Padmanabhan, May E. Montasser, Jeff R. O’Connell, Kathleen Ryan, Alan R. Shuldiner, Stefanie Aeschbacher, David Conen, Lorenz Risch, Sébastien Thériault, Nina Hutri-Kähönen, Terho Lehtimäki, Leo-Pekka Lyytikäinen, Olli T. Raitakari, Catriona L. K. Barnes, Harry Campbell, Peter K. Joshi, James F. Wilson, Aaron Isaacs, Jan A. Kors, Cornelia M. van Duijn, Paul L. Huang, Vilmundur Gudnason, Tamara B. Harris, Lenore J. Launer, Albert V. Smith, Erwin P. Bottinger, Ruth J. F. Loos, Girish N. Nadkarni, Michael H. Preuss, Adolfo Correa, Hao Mei, James Wilson, Thomas Meitinger, Martina Müller-Nurasyid, Annette Peters, Melanie Waldenberger, Massimo Mangino, Timothy D. Spector, Michiel Rienstra, Yordi J. van de Vegte, Pim van der Harst, Niek Verweij, Stefan Kääb, Katharina Schramm, Moritz F. Sinner, Konstantin Strauch, Michael J. Cutler, Diane Fatkin, Barry London, Morten Olesen, Dan M. Roden, M. Benjamin Shoemaker, J. Gustav Smith, Mary L. Biggs, Joshua C. Bis, Jennifer A. Brody, Bruce M. Psaty, Kenneth Rice, Nona Sotoodehnia, Alessandro De Grandi, Christian Fuchsberger, Cristian Pattaro, Peter P. Pramstaller, Ian Ford, J. Wouter Jukema, Peter W. Macfarlane, Stella Trompet, Marcus Dörr, Stephan B. Felix, Uwe Völker, Stefan Weiss, Aki S. Havulinna, Antti Jula, Katri Sääksjärvi, Veikko Salomaa, Xiuqing Guo, Susan R. Heckbert, Henry J. Lin, Jerome I. Rotter, Kent D. Taylor, Jie Yao, Renée de Mutsert, Arie C. Maan, Dennis O. Mook-Kanamori, Raymond Noordam, Francesco Cucca, Jun Ding, Edward G. Lakatta, Yong Qian, Kirill V. Tarasov, Daniel Levy, Honghuang Lin, Christopher H. Newton-Cheh, Kathryn L. Lunetta, Alison D. Murray, David J. Porteous, Blair H. Smith, Bruno H. Stricker, André Uitterlinden, Marten E. van den Berg, Jeffrey Haessler, Rebecca D. Jackson, Charles Kooperberg, Ulrike Peters, Alexander P. Reiner, Eric A. Whitsel, Alvaro Alonso, Dan E. Arking, Eric Boerwinkle, Georg B. Ehret, Elsayed Z. Soliman, Christy L. Avery, Stephanie M. Gogarten, Kathleen F. Kerr, Cathy C. Laurie, Amanda A. Seyerle, Adrienne Stilp, Solmaz Assa, M. Abdullah Said, M. Yldau van der Ende, Pier D. Lambiase, Michele Orini, Julia Ramirez, Stefan Van Duijvenboden, David O. Arnar, Daniel F. Gudbjartsson, Hilma Holm, Patrick Sulem, Gudmar Thorleifsson, Rosa B. Thorolfsdottir, Unnur Thorsteinsdottir, Emelia J. Benjamin, Andrew Tinker, Kari Stefansson, Patrick T. Ellinor, Yalda Jamshidi, Steven A. Lubitz, and Patricia B. Munroe
Subjects: Science
Abstract: On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
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38. GAME-ON: A Multimodal Dataset for Cohesion and Group Analysis

Author: Lucien Maman, Eleonora Ceccaldi, Nale Lehmann-Willenbrock, Laurence Likforman-Sulem, Mohamed Chetouani, Gualtiero Volpe, and Giovanna Varni
Subjects: Cohesion, group interaction analysis, multimodal dataset, social signal processing, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract: This paper presents GAME-ON (Group Analysis of Multimodal Expression of cohesiON), a multimodal dataset specifically designed for studying group cohesion and for explicitly controlling its variation over time. Cohesion is here addressed according to the Severt and Estrada's theoretical multidimensional integrative framework. More specifically, GAME-ON focuses on the social and task dimensions of the instrumental function of cohesion. The dataset consists of over 11 hours of synchronized multimodal recordings (audio, video, and motion capture data) of 17 small groups (3 persons) playing a social game, i.e., an escape game. The game consists of several tasks designed to manipulate the variation of cohesion over time. GAME-ON includes annotations consisting of self-assessment of cohesion and other constructs such as emotions, leadership, and warmth and competence. A first statistical analysis of these annotations shows that we successfully manipulated all the relative variations of cohesion (between tasks) over time. This holds for all tasks except for one where we observed a significant variation of cohesion in the opposite direction than expected. The dataset will be publicly available for research purposes. The motivation of our work is to provide the scientific community with an asset for studying cohesion and other group phenomena.
Published: 2020
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39. Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis

Author: Thorunn A. Olafsdottir, Fannar Theodors, Kristbjorg Bjarnadottir, Unnur Steina Bjornsdottir, Arna B. Agustsdottir, Olafur A. Stefansson, Erna V. Ivarsdottir, Jon K. Sigurdsson, Stefania Benonisdottir, Gudmundur I. Eyjolfsson, David Gislason, Thorarinn Gislason, Steinunn Guðmundsdóttir, Arnaldur Gylfason, Bjarni V. Halldorsson, Gisli H. Halldorsson, Thorhildur Juliusdottir, Anna M. Kristinsdottir, Dora Ludviksdottir, Bjorn R. Ludviksson, Gisli Masson, Kristjan Norland, Pall T. Onundarson, Isleifur Olafsson, Olof Sigurdardottir, Lilja Stefansdottir, Gardar Sveinbjornsson, Vinicius Tragante, Daniel F. Gudbjartsson, Gudmar Thorleifsson, Patrick Sulem, Unnur Thorsteinsdottir, Gudmundur L. Norddahl, Ingileif Jonsdottir, and Kari Stefansson
Subjects: Science
Abstract: Asthma is a common allergic airway disease with significant inter-individual heterogeneity. Here, Olafsdottir et al. report a genome-wide meta-analysis of two large population-based cohorts to identify sequence variants that associate with asthma risk and perform follow-up functional analyses on a protective loss-of-function variant in TNFRSF8.
Published: 2020
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40. Comparative study of anthocyanin extraction methods in Dahlia pinnata petals

Author: Sulem Yali Granados-Balbuena, Vanesa Chicatto-Gasperín, Lucía Aztatzi-Rugerio, Ericka Santacruz-Juárez, Raúl René Robles-de la Torre, Erik Ocaranza-Sánchez, and María Reyna Robles-López
Subjects: Plant culture, SB1-1110, Botany, QK1-989
Abstract: Anthocyanins are phenolic compounds responsible for the color of numerous plant sources. In literature, there is little information about the dahlia flower as a potential source of anthocyanins. This study aimed to develop a procedure for anthocyanins extraction from black dahlia petals using fresh and dehydrated material. A three-stages nested design was used to develop the methodology, 3 solid-liquid-ratios and 6 dissolvents nested in 3 methods. The highest yields were obtained with the homogenization assisted maceration technique, citric acid solvent (2, 4, 6%), and a ratio of 1:30 with dry petals. The results of this study show the opportunity to obtain a high anthocyanin content from black dahlia and open the possibility to use it as another important source of this pigment.
Published: 2022
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41. A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease

Author: Gudny A. Arnadottir, Gudmundur L. Norddahl, Steinunn Gudmundsdottir, Arna B. Agustsdottir, Snaevar Sigurdsson, Brynjar O. Jensson, Kristbjorg Bjarnadottir, Fannar Theodors, Stefania Benonisdottir, Erna V. Ivarsdottir, Asmundur Oddsson, Ragnar P. Kristjansson, Gerald Sulem, Kristjan F. Alexandersson, Thorhildur Juliusdottir, Kjartan R. Gudmundsson, Jona Saemundsdottir, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Asgeir Sigurdsson, Paolo Manzanillo, Sigurjon A. Gudjonsson, Gudmundur A. Thorisson, Olafur Th. Magnusson, Gisli Masson, Kjartan B. Orvar, Hilma Holm, Sigurdur Bjornsson, Reynir Arngrimsson, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Ingileif Jonsdottir, Asgeir Haraldsson, Patrick Sulem, and Kari Stefansson
Subjects: Science
Abstract: Mutations in genes encoding NAPDH oxidase subunits are known to be causative for the primary immunodeficiency chronic granulomatous disease (CGD). Here, the authors identify CYBC1 mutations in patients with CGD and show that CYBC1 is important for formation of the NADPH complex and respiratory burst.
Published: 2018
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42. Sequence variants with large effects on cardiac electrophysiology and disease

Author: Kristjan Norland, Gardar Sveinbjornsson, Rosa B. Thorolfsdottir, Olafur B. Davidsson, Vinicius Tragante, Sridharan Rajamani, Anna Helgadottir, Solveig Gretarsdottir, Jessica van Setten, Folkert W. Asselbergs, Jon Th. Sverrisson, Sigurdur S. Stephensen, Gylfi Oskarsson, Emil L. Sigurdsson, Karl Andersen, Ragnar Danielsen, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, David O. Arnar, Patrick Sulem, Hilma Holm, Daniel F. Gudbjartsson, and Kari Stefansson
Subjects: Science
Abstract: Aberrant morphology of the QRS complex in an electrocardiogram can be associated with cardiac morbidity and mortality. Here, the authors perform genome-wide association studies for ten measures of the QRS complex in 81,192 individuals and find 86 previously unreported loci that associate with at least one parameter.
Published: 2019
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43. Associations of autozygosity with a broad range of human phenotypes

Author: David W Clark, Yukinori Okada, Kristjan H S Moore, Dan Mason, Nicola Pirastu, Ilaria Gandin, Hannele Mattsson, Catriona L K Barnes, Kuang Lin, Jing Hua Zhao, Patrick Deelen, Rebecca Rohde, Claudia Schurmann, Xiuqing Guo, Franco Giulianini, Weihua Zhang, Carolina Medina-Gomez, Robert Karlsson, Yanchun Bao, Traci M Bartz, Clemens Baumbach, Ginevra Biino, Matthew J Bixley, Marco Brumat, Jin-Fang Chai, Tanguy Corre, Diana L Cousminer, Annelot M Dekker, David A Eccles, Kristel R van Eijk, Christian Fuchsberger, He Gao, Marine Germain, Scott D Gordon, Hugoline G de Haan, Sarah E Harris, Edith Hofer, Alicia Huerta-Chagoya, Catherine Igartua, Iris E Jansen, Yucheng Jia, Tim Kacprowski, Torgny Karlsson, Marcus E Kleber, Shengchao Alfred Li, Ruifang Li-Gao, Anubha Mahajan, Koichi Matsuda, Karina Meidtner, Weihua Meng, May E Montasser, Peter J van der Most, Matthias Munz, Teresa Nutile, Teemu Palviainen, Gauri Prasad, Rashmi B Prasad, Tallapragada Divya Sri Priyanka, Federica Rizzi, Erika Salvi, Bishwa R Sapkota, Daniel Shriner, Line Skotte, Melissa C Smart, Albert Vernon Smith, Ashley van der Spek, Cassandra N Spracklen, Rona J Strawbridge, Salman M Tajuddin, Stella Trompet, Constance Turman, Niek Verweij, Clara Viberti, Lihua Wang, Helen R Warren, Robyn E Wootton, Lisa R Yanek, Jie Yao, Noha A Yousri, Wei Zhao, Adebowale A Adeyemo, Saima Afaq, Carlos Alberto Aguilar-Salinas, Masato Akiyama, Matthew L Albert, Matthew A Allison, Maris Alver, Tin Aung, Fereidoun Azizi, Amy R Bentley, Heiner Boeing, Eric Boerwinkle, Judith B Borja, Gert J de Borst, Erwin P Bottinger, Linda Broer, Harry Campbell, Stephen Chanock, Miao-Li Chee, Guanjie Chen, Yii-Der I Chen, Zhengming Chen, Yen-Feng Chiu, Massimiliano Cocca, Francis S Collins, Maria Pina Concas, Janie Corley, Giovanni Cugliari, Rob M van Dam, Anna Damulina, Maryam S Daneshpour, Felix R Day, Graciela E Delgado, Klodian Dhana, Alexander S F Doney, Marcus Dörr, Ayo P Doumatey, Nduna Dzimiri, S Sunna Ebenesersdóttir, Joshua Elliott, Paul Elliott, Ralf Ewert, Janine F Felix, Krista Fischer, Barry I Freedman, Giorgia Girotto, Anuj Goel, Martin Gögele, Mark O Goodarzi, Mariaelisa Graff, Einat Granot-Hershkovitz, Francine Grodstein, Simonetta Guarrera, Daniel F Gudbjartsson, Kamran Guity, Bjarni Gunnarsson, Yu Guo, Saskia P Hagenaars, Christopher A Haiman, Avner Halevy, Tamara B Harris, Mehdi Hedayati, David A van Heel, Makoto Hirata, Imo Höfer, Chao Agnes Hsiung, Jinyan Huang, Yi-Jen Hung, M Arfan Ikram, Anuradha Jagadeesan, Pekka Jousilahti, Yoichiro Kamatani, Masahiro Kanai, Nicola D Kerrison, Thorsten Kessler, Kay-Tee Khaw, Chiea Chuen Khor, Dominique P V de Kleijn, Woon-Puay Koh, Ivana Kolcic, Peter Kraft, Bernhard K Krämer, Zoltán Kutalik, Johanna Kuusisto, Claudia Langenberg, Lenore J Launer, Deborah A Lawlor, I-Te Lee, Wen-Jane Lee, Markus M Lerch, Liming Li, Jianjun Liu, Marie Loh, Stephanie J London, Stephanie Loomis, Yingchang Lu, Jian’an Luan, Reedik Mägi, Ani W Manichaikul, Paolo Manunta, Gísli Másson, Nana Matoba, Xue W Mei, Christa Meisinger, Thomas Meitinger, Massimo Mezzavilla, Lili Milani, Iona Y Millwood, Yukihide Momozawa, Amy Moore, Pierre-Emmanuel Morange, Hortensia Moreno-Macías, Trevor A Mori, Alanna C Morrison, Taulant Muka, Yoshinori Murakami, Alison D Murray, Renée de Mutsert, Josyf C Mychaleckyj, Mike A Nalls, Matthias Nauck, Matt J Neville, Ilja M Nolte, Ken K Ong, Lorena Orozco, Sandosh Padmanabhan, Gunnar Pálsson, James S Pankow, Cristian Pattaro, Alison Pattie, Ozren Polasek, Neil Poulter, Peter P Pramstaller, Lluis Quintana-Murci, Katri Räikkönen, Sarju Ralhan, Dabeeru C Rao, Wouter van Rheenen, Stephen S Rich, Paul M Ridker, Cornelius A Rietveld, Antonietta Robino, Frank J A van Rooij, Daniela Ruggiero, Yasaman Saba, Charumathi Sabanayagam, Maria Sabater-Lleal, Cinzia Felicita Sala, Veikko Salomaa, Kevin Sandow, Helena Schmidt, Laura J Scott, William R Scott, Bahareh Sedaghati-Khayat, Bengt Sennblad, Jessica van Setten, Peter J Sever, Wayne H-H Sheu, Yuan Shi, Smeeta Shrestha, Sharvari Rahul Shukla, Jon K Sigurdsson, Timo Tonis Sikka, Jai Rup Singh, Blair H Smith, Alena Stančáková, Alice Stanton, John M Starr, Lilja Stefansdottir, Leon Straker, Patrick Sulem, Gardar Sveinbjornsson, Morris A Swertz, Adele M Taylor, Kent D Taylor, Natalie Terzikhan, Yih-Chung Tham, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Annika Tillander, Russell P Tracy, Teresa Tusié-Luna, Ioanna Tzoulaki, Simona Vaccargiu, Jagadish Vangipurapu, Jan H Veldink, Veronique Vitart, Uwe Völker, Eero Vuoksimaa, Salma M Wakil, Melanie Waldenberger, Gurpreet S Wander, Ya Xing Wang, Nicholas J Wareham, Sarah Wild, Chittaranjan S Yajnik, Jian-Min Yuan, Lingyao Zeng, Liang Zhang, Jie Zhou, Najaf Amin, Folkert W Asselbergs, Stephan J L Bakker, Diane M Becker, Benjamin Lehne, David A Bennett, Leonard H van den Berg, Sonja I Berndt, Dwaipayan Bharadwaj, Lawrence F Bielak, Murielle Bochud, Mike Boehnke, Claude Bouchard, Jonathan P Bradfield, Jennifer A Brody, Archie Campbell, Shai Carmi, Mark J Caulfield, David Cesarini, John C Chambers, Giriraj Ratan Chandak, Ching-Yu Cheng, Marina Ciullo, Marilyn Cornelis, Daniele Cusi, George Davey Smith, Ian J Deary, Rajkumar Dorajoo, Cornelia M van Duijn, David Ellinghaus, Jeanette Erdmann, Johan G Eriksson, Evangelos Evangelou, Michele K Evans, Jessica D Faul, Bjarke Feenstra, Mary Feitosa, Sylvain Foisy, Andre Franke, Yechiel Friedlander, Paolo Gasparini, Christian Gieger, Clicerio Gonzalez, Philippe Goyette, Struan F A Grant, Lyn R Griffiths, Leif Groop, Vilmundur Gudnason, Ulf Gyllensten, Hakon Hakonarson, Anders Hamsten, Pim van der Harst, Chew-Kiat Heng, Andrew A Hicks, Hagit Hochner, Heikki Huikuri, Steven C Hunt, Vincent W V Jaddoe, Philip L De Jager, Magnus Johannesson, Åsa Johansson, Jost B Jonas, J Wouter Jukema, Juhani Junttila, Jaakko Kaprio, Sharon L. R. Kardia, Fredrik Karpe, Meena Kumari, Markku Laakso, Sander W van der Laan, Jari Lahti, Matthias Laudes, Rodney A Lea, Wolfgang Lieb, Thomas Lumley, Nicholas G Martin, Winfried März, Giuseppe Matullo, Mark I McCarthy, Sarah E Medland, Tony R Merriman, Andres Metspalu, Brian F Meyer, Karen L Mohlke, Grant W Montgomery, Dennis Mook-Kanamori, Patricia B Munroe, Kari E North, Dale R Nyholt, Jeffery R O’connell, Carole Ober, Albertine J Oldehinkel, Walter Palmas, Colin Palmer, Gerard G Pasterkamp, Etienne Patin, Craig E Pennell, Louis Perusse, Patricia A Peyser, Mario Pirastu, Tinca J. C. Polderman, David J Porteous, Danielle Posthuma, Bruce M Psaty, John D Rioux, Fernando Rivadeneira, Charles Rotimi, Jerome I Rotter, Igor Rudan, Hester M Den Ruijter, Dharambir K Sanghera, Naveed Sattar, Reinhold Schmidt, Matthias B Schulze, Heribert Schunkert, Robert A Scott, Alan R Shuldiner, Xueling Sim, Neil Small, Jennifer A Smith, Nona Sotoodehnia, E-Shyong Tai, Alexander Teumer, Nicholas J Timpson, Daniela Toniolo, David-Alexandre Tregouet, Tiinamaija Tuomi, Peter Vollenweider, Carol A Wang, David R Weir, John B Whitfield, Cisca Wijmenga, Tien-Yin Wong, John Wright, Jingyun Yang, Lei Yu, Babette S Zemel, Alan B Zonderman, Markus Perola, Patrik K. E. Magnusson, André G Uitterlinden, Jaspal S Kooner, Daniel I Chasman, Ruth J. F. Loos, Nora Franceschini, Lude Franke, Chris S Haley, Caroline Hayward, Robin G Walters, John R. B. Perry, Tōnu Esko, Agnar Helgason, Kari Stefansson, Peter K Joshi, Michiaki Kubo, and James F Wilson
Subjects: Science
Abstract: Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.
Published: 2019
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44. GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures

Author: Unnur Styrkarsdottir, Olafur A. Stefansson, Kristbjorg Gunnarsdottir, Gudmar Thorleifsson, Sigrun H. Lund, Lilja Stefansdottir, Kristinn Juliusson, Arna B. Agustsdottir, Florian Zink, Gisli H. Halldorsson, Erna V. Ivarsdottir, Stefania Benonisdottir, Hakon Jonsson, Arnaldur Gylfason, Kristjan Norland, Katerina Trajanoska, Cindy G. Boer, Lorraine Southam, Jason C. S. Leung, Nelson L. S. Tang, Timothy C. Y. Kwok, Jenny S. W. Lee, Suzanne C. Ho, Inger Byrjalsen, Jacqueline R. Center, Seung Hun Lee, Jung-Min Koh, L. Stefan Lohmander, Lan T. Ho-Pham, Tuan V. Nguyen, John A. Eisman, Jean Woo, Ping-C. Leung, John Loughlin, Eleftheria Zeggini, Claus Christiansen, Fernando Rivadeneira, Joyce van Meurs, Andre G. Uitterlinden, Brynjolfur Mogensen, Helgi Jonsson, Thorvaldur Ingvarsson, Gunnar Sigurdsson, Rafn Benediktsson, Patrick Sulem, Ingileif Jonsdottir, Gisli Masson, Hilma Holm, Gudmundur L. Norddahl, Unnur Thorsteinsdottir, Daniel F. Gudbjartsson, and Kari Stefansson
Subjects: Science
Abstract: Size and shape of bones are important for height and body shape. Here, Styrkarsdottir et al identify 12 loci in a GWAS for bone area derived from DXA scans and show that these loci associate with other bone-related phenotypes including osteoarthritis, height, bone mineral density and risk of hip fracture.
Published: 2019
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45. A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy

Author: Gyda Bjornsdottir, Erna V. Ivarsdottir, Kristbjorg Bjarnadottir, Stefania Benonisdottir, Sandra Sif Gylfadottir, Gudny A. Arnadottir, Rafn Benediktsson, Gisli Hreinn Halldorsson, Anna Helgadottir, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Ingileif Jonsdottir, Anna Margret Kristinsdottir, Olafur Th. Magnusson, Gisli Masson, Pall Melsted, Thorunn Rafnar, Asgeir Sigurdsson, Gunnar Sigurdsson, Astros Skuladottir, Valgerdur Steinthorsdottir, Unnur Styrkarsdottir, Gudmundur Thorgeirsson, Gudmar Thorleifsson, Arnor Vikingsson, Daniel F. Gudbjartsson, Hilma Holm, Hreinn Stefansson, Unnur Thorsteinsdottir, Gudmundur L. Norddahl, Patrick Sulem, Thorgeir E. Thorgeirsson, and Kari Stefansson
Subjects: Science
Abstract: Diagnosis and classification of peripheral neuropathy (PN) is facilitated by nerve conduction (NC) studies. Here, Bjornsdottir et al. find a low-frequency PRPH splice-donor variant that associates with NC amplitude and neurological assessment of recalled PRPH variant carriers reveals increased risk of a mild sensory-negative PN.
Published: 2019
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46. Sequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density

Author: Erna V. Ivarsdottir, Stefania Benonisdottir, Gudmar Thorleifsson, Patrick Sulem, Asmundur Oddsson, Unnur Styrkarsdottir, Snaedis Kristmundsdottir, Gudny A. Arnadottir, Gudmundur Thorgeirsson, Ingileif Jonsdottir, Gunnar M. Zoega, Unnur Thorsteinsdottir, Daniel F. Gudbjartsson, Fridbert Jonasson, Hilma Holm, and Kari Stefansson
Subjects: Science
Abstract: The corneal endothelium is crucial for proper vision. Here, Ivarsdottir et al. perform genome-wide association studies for various corneal endothelial cell measurements and find that an intergenic variant near ANAPC1 explains 24% of the variance of endothelial cell density and associates with corneal hysteresis.
Published: 2019
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47. Simple discrete-time self-exciting models can describe complex dynamic processes: A case study of COVID-19.

Author: Raiha Browning, Deborah Sulem, Kerrie Mengersen, Vincent Rivoirard, and Judith Rousseau
Subjects: Medicine, Science
Abstract: Hawkes processes are a form of self-exciting process that has been used in numerous applications, including neuroscience, seismology, and terrorism. While these self-exciting processes have a simple formulation, they can model incredibly complex phenomena. Traditionally Hawkes processes are a continuous-time process, however we enable these models to be applied to a wider range of problems by considering a discrete-time variant of Hawkes processes. We illustrate this through the novel coronavirus disease (COVID-19) as a substantive case study. While alternative models, such as compartmental and growth curve models, have been widely applied to the COVID-19 epidemic, the use of discrete-time Hawkes processes allows us to gain alternative insights. This paper evaluates the capability of discrete-time Hawkes processes by modelling daily mortality counts as distinct phases in the COVID-19 outbreak. We first consider the initial stage of exponential growth and the subsequent decline as preventative measures become effective. We then explore subsequent phases with more recent data. Various countries that have been adversely affected by the epidemic are considered, namely, Brazil, China, France, Germany, India, Italy, Spain, Sweden, the United Kingdom and the United States. These countries are all unique concerning the spread of the virus and their corresponding response measures. However, we find that this simple model is useful in accurately capturing the dynamics of the process, despite hidden interactions that are not directly modelled due to their complexity, and differences both within and between countries. The utility of this model is not confined to the current COVID-19 epidemic, rather this model could explain many other complex phenomena. It is of interest to have simple models that adequately describe these complex processes with unknown dynamics. As models become more complex, a simpler representation of the process can be desirable for the sake of parsimony.
Published: 2021
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48. COPA syndrome in an Icelandic family caused by a recurrent missense mutation in COPA

Author: Brynjar O. Jensson, Sif Hansdottir, Gudny A. Arnadottir, Gerald Sulem, Ragnar P. Kristjansson, Asmundur Oddsson, Stefania Benonisdottir, Hakon Jonsson, Agnar Helgason, Jona Saemundsdottir, Olafur T. Magnusson, Gisli Masson, Gudmundur A. Thorisson, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Asgeir Sigurdsson, Ingileif Jonsdottir, Vigdis Petursdottir, Jon R. Kristinsson, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Reynir Arngrimsson, Patrick Sulem, Gunnar Gudmundsson, and Kari Stefansson
Subjects: COPA syndrome, Lung disease, Arthritis, Immune dysregulation, Case report, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract: Abstract Background Rare missense mutations in the gene encoding coatomer subunit alpha (COPA) have recently been shown to cause autoimmune interstitial lung, joint and kidney disease, also known as COPA syndrome, under a dominant mode of inheritance. Case presentation Here we describe an Icelandic family with three affected individuals over two generations with a rare clinical presentation of lung and joint disease and a histological diagnosis of follicular bronchiolitis. We performed whole-genome sequencing (WGS) of the three affected as well as three unaffected members of the family, and searched for rare genotypes associated with disease using 30,067 sequenced Icelanders as a reference population. We assessed all coding and splicing variants, prioritizing variants in genes known to cause interstitial lung disease. We detected a heterozygous missense mutation, p.Glu241Lys, in the COPA gene, private to the affected family members. The mutation occurred de novo in the paternal germline of the index case and was absent from 30,067 Icelandic genomes and 141,353 individuals from the genome Aggregation Database (gnomAD). The mutation occurs within the conserved and functionally important WD40 domain of the COPA protein. Conclusions This is the second report of the p.Glu241Lys mutation in COPA, indicating the recurrent nature of the mutation. The mutation was reported to co-segregate with COPA syndrome in a large family from the USA with five affected members, and classified as pathogenic. The two separate occurrences of the p.Glu241Lys mutation in cases and its absence from a large number of sequenced genomes confirms its role in the pathogenesis of the COPA syndrome.
Published: 2017
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49. Compound heterozygous mutations in UBA5 causing early-onset epileptic encephalopathy in two sisters

Author: Gudny A. Arnadottir, Brynjar O. Jensson, Sigurdur E. Marelsson, Gerald Sulem, Asmundur Oddsson, Ragnar P. Kristjansson, Stefania Benonisdottir, Sigurjon A. Gudjonsson, Gisli Masson, Gudmundur A. Thorisson, Jona Saemundsdottir, Olafur Th. Magnusson, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Asgeir Sigurdsson, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Reynir Arngrimsson, Patrick Sulem, and Kari Stefansson
Subjects: Epileptic encephalopathy, UBA5, Hypomorphic mutation, Exonic splicing mutation, Ufmylation, Case report, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract: Abstract Background Epileptic encephalopathies are a group of childhood epilepsies that display high phenotypic and genetic heterogeneity. The recent, extensive use of next-generation sequencing has identified a large number of genes in epileptic encephalopathies, including UBA5 in which biallelic mutations were first described as pathogenic in 2016 (Colin E et al., Am J Hum Genet 99(3):695-703, 2016. Muona M et al., Am J Hum Genet 99(3):683-694, 2016). UBA5 encodes an activating enzyme for a post-translational modification mechanism known as ufmylation, and is the first gene from the ufmylation pathway that is linked to disease. Case presentation We sequenced the genomes of two sisters with early-onset epileptic encephalopathy along with their unaffected parents in an attempt to find a genetic cause for their condition. The sisters, born in 2004 and 2006, presented with infantile spasms at six months of age, which later progressed to recurrent, treatment-resistant seizures. We detected a compound heterozygous genotype in UBA5 in the sisters, a genotype not seen elsewhere in an Icelandic reference set of 30,067 individuals nor in public databases. One of the mutations, c.684G > A, is a paternally inherited exonic splicing mutation, occuring at the last nucleotide of exon 7 of UBA5. The mutation is predicted to disrupt the splice site, resulting in loss-of-function of one allele of UBA5. The second mutation is a maternally inherited missense mutation, p.Ala371Thr, previously reported as pathogenic when in compound heterozygosity with a loss-of-function mutation in UBA5 and is believed to produce a hypomorphic allele. Supportive of this, we have identified three adult Icelanders homozygous for the p.Ala371Thr mutation who show no signs of neurological disease. Conclusions We describe compound heterozygous mutations in the UBA5 gene in two sisters with early-onset epileptic encephalopathy. To our knowledge, this is the first description of mutations in UBA5 since the initial discovery that pathogenic biallelic variants in the gene cause early-onset epileptic encephalopathy. We further provide confirmatory evidence that p.Ala371Thr is a hypomorphic mutation, by presenting three adult homozygotes who show no signs of neurological disease.
Published: 2017
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50. Genome-wide association meta-analysis yields 20 loci associated with gallstone disease

Author: Egil Ferkingstad, Asmundur Oddsson, Solveig Gretarsdottir, Stefania Benonisdottir, Gudmar Thorleifsson, Aimee M. Deaton, Stefan Jonsson, Olafur A. Stefansson, Gudmundur L. Norddahl, Florian Zink, Gudny A. Arnadottir, Bjarni Gunnarsson, Gisli H. Halldorsson, Anna Helgadottir, Brynjar O. Jensson, Ragnar P. Kristjansson, Gardar Sveinbjornsson, David A. Sverrisson, Gisli Masson, Isleifur Olafsson, Gudmundur I. Eyjolfsson, Olof Sigurdardottir, Hilma Holm, Ingileif Jonsdottir, Sigurdur Olafsson, Thora Steingrimsdottir, Thorunn Rafnar, Einar S. Bjornsson, Unnur Thorsteinsdottir, Daniel F. Gudbjartsson, Patrick Sulem, and Kari Stefansson
Subjects: Science
Abstract: Genome-wide association studies have so far identified eight risk loci for gallstone disease. Here, the authors perform meta-analysis in cohorts from Iceland and the UK which reveals further 21 common and low-frequency risk variants that highlight the role of bile acid homeostasis in gallstone disease.
Published: 2018
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