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2. The Xylella fastidosa RTX operons: evidence for the evolution of protein mosaics through novel genetic exchanges

Author

Gregory A. Gambetta, Mark A. Matthews, and Michael Syvanen

Subjects
Hemolysin, Pierce’s disease, Horizontal gene transfer, Lateral gene transfer, Orphan, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Xylella fastidiosa (Xf) is a gram negative bacterium inhabiting the plant vascular system. In most species this bacterium lives as a benign symbiote, but in several agriculturally important plants (e.g. coffee, citrus, grapevine) Xf is pathogenic. Xf has four loci encoding homologues to hemolysin RTX proteins, virulence factors involved in a wide range of plant pathogen interactions. Results We show that all four genes are expressed during pathogenesis in grapevine. The sequences from these four genes have a complex repetitive structure. At the C-termini, sequence diversity between strains is what would be expected from orthologous genes. However, within strains there is no N-terminal homology, indicating these loci encode RTXs of different functions and/or specificities. More striking is that many of the orthologous loci between strains share this extreme variation at the N-termini. Thus these RTX orthologues are most easily visualized as fusions between the orthologous C–termini and different N-termini. Further, the four genes are found in operons having a peculiar structure with an extensively duplicated module encoding a small protein with homology to the N-terminal region of the full length RTX. Surprisingly, some of these small peptides are most similar not to their corresponding full length RTX, but to the N-termini of RTXs from other Xf strains, and even other remotely related species. Conclusions These results demonstrate that these genes are expressed in planta during pathogenesis. Their structure suggests extensive evolutionary restructuring through horizontal gene transfers and heterologous recombination mechanisms. The sum of the evidence suggests these repetitive modules are a novel kind of mobile genetic element.

Published
2018
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4. Murine type II Abeta fibril from ARTE10 mouse

Author

Zielinski, M., primary, Peralta Reyes, F.S., additional, Gremer, L., additional, Schemmert, S., additional, Frieg, B., additional, Willuweit, A., additional, Donner, L., additional, Elvers, M., additional, Nilsson, L.N.G., additional, Syvanen, S., additional, Sehlin, D., additional, Ingelsson, M., additional, Willbold, D., additional, and Schroeder, G.F., additional

Published
2023
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5. DI1 Abeta fibril from tg-SwDI mouse

Author

Zielinski, M., primary, Peralta Reyes, F.S., additional, Gremer, L., additional, Schemmert, S., additional, Frieg, B., additional, Willuweit, A., additional, Donner, L., additional, Elvers, M., additional, Nilsson, L.N.G., additional, Syvanen, S., additional, Sehlin, D., additional, Ingelsson, M., additional, Willbold, D., additional, and Schroeder, G.F., additional

Published
2023
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6. Surgical and Health-related Quality of life Outcomes in Children With Congenital Scoliosis During 5-year Follow-up. Comparison to Age and Sex-matched Healthy Controls

Author

Haapala, Hermanni, Heiskanen, Susanna, Syvanen, Johanna, Raitio, Arimatias, Helenius, Linda, Ahonen, Matti, Diarbakerli, Elias, Gerdhem, Paul, Helenius, Ilkka, Haapala, Hermanni, Heiskanen, Susanna, Syvanen, Johanna, Raitio, Arimatias, Helenius, Linda, Ahonen, Matti, Diarbakerli, Elias, Gerdhem, Paul, and Helenius, Ilkka

Abstract

Background:Congenital spinal anomalies represent a heterogeneous group of spinal deformities, of which only progressive or severe curves warrant surgical management. Only a limited number of studies have investigated the impact of surgery on the health-related quality of life and very limited data exists comparing these outcomes to healthy controls. Methods:A single surgeon series of 67 consecutive children with congenital scoliosis (mean age at surgery 8.0 y, range: 1.0 to 18.3 y, 28 girls) undergoing hemivertebrectomy (n = 34), instrumented spinal fusion (n = 20), or vertical expandable prosthetic titanium rib procedure (n = 13) with a mean follow-up of 5.8 years (range: 2 to 13 y). The comparison was made to age and sex-matched healthy controls. Outcome measures included the Scoliosis Research Society questionnaire both pre and postoperatively, radiographic outcomes, and complications. Results:The average major curve correction was significantly better in the hemivertebrectomy (60%) and instrumented spinal fusion (51%) than in the vertical expandable prosthetic titanium rib group (24%), respectively (P < 0.001). Complications were noted in 8 of 67 (12%) children, but all patients recovered fully during follow-up. Pain, self-image, and function domains improved numerically from preoperative to final follow-up, but the pain score was the only one with a statistically significant change (P = 0.033). The Scoliosis Research Society pain, self-image, and function domain scores remained at a significantly lower level at the final follow-up than in the healthy controls (P <= 0.05), while activity scores improved to a similar level. Conclusions:Surgery for congenital scoliosis improved angular spinal deformities with a reasonable risk of complications. Health-related quality of life outcomes improved from preoperative to final follow-up, but especially pain and function domains remained at a significantly lower level than in the age and sex-matched healthy controls.

Published
2023
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7. Back Pain and Quality of Life 10 Years After Segmental Pedicle Screw Instrumentation for Adolescent Idiopathic Scoliosis

Author

Ahonen, Matti, Syvanen, Johanna, Helenius, Linda, Mattila, Mikko, Perokorpi, Tanja, Diarbakerli, Elias, Gerdhem, Paul, Helenius, Ilkka, Ahonen, Matti, Syvanen, Johanna, Helenius, Linda, Mattila, Mikko, Perokorpi, Tanja, Diarbakerli, Elias, Gerdhem, Paul, and Helenius, Ilkka

Abstract

Study Design.Comparative cohort study. Objective.The aim of the present study was to evaluate pain and health-related quality of life (HRQoL) in surgically managed patients with a minimum follow-up of 10 years compared with patients with untreated adolescent idiopathic scoliosis (AIS) and a healthy control group. Summary of Background Data.Posterior spinal fusion with pedicle screws is the standard treatment for AIS, although it remains unclear whether this procedure results in improved long-term HRQoL compared with untreated patients with AIS. Patients and Methods.Sixty-four consecutive patients at a minimum follow-up of 10 years, who underwent posterior pedicle screw instrumentation for AIS were prospectively enrolled. Fifty-three (83%) of these patients completed Scoliosis Research Society (SRS) 24 questionnaires, clinical examination, and standing spinal radiographs. Pain and HRQoL were compared with age and sex-matched patients with untreated AIS and healthy individuals. Results.The mean major curve was 57 degrees preoperatively and 15 degrees at the 10-year follow-up. SRS-24 self-image domain score showed a significant improvement from preoperative to 2 years and remained significantly better at the 10-year follow-up (P < 0.001). Patients fused to L3 or below had lower pain, satisfaction, and total score than patients fused to L2 or above (P < 0.05), but self-image, function, and activity scores did not differ between groups at 10-year follow-up. Pain, self-image, general activity, and total SRS domains were significantly better at 10-year follow-up in the surgically treated patients as compared with untreated patients (all P < 0.05). Healthy controls had significantly higher total scores than those surgically treated at 10-year follow-ups (P < 0.001). Conclusion.Patients undergoing segmental pedicle screw instrumentation for AIS maintain high-level HRQoL during a 10-year follow-up. Their HRQoL was significantly better than in the untreated patient

Published
2023
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9. A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol

Author

Surakka, Ida, Whitfield, John B, Perola, Markus, Visscher, Peter M, Montgomery, Grant W, Falchi, Mario, Willemsen, Gonneke, de Geus, Eco JC, Magnusson, Patrik KE, Christensen, Kaare, Sorensen, Thorkild IA, Pietilainen, Kirsi H, Rantanen, Taina, Silander, Kaisa, Widen, Elisabeth, Muilu, Juha, Rahman, Iffat, Liljedahl, Ulrika, Syvanen, Ann-Christine, Palotie, Aarno, Kaprio, Jaakko, Kyvik, Kirsten O, Pedersen, Nancy L, Boomsma, Dorret I, Spector, Tim, Martin, Nicholas G, Ripatti, Samuli, and Peltonen, Leena

Published
2012

12. Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases

Author

Lundtoft, Christian, Pucholt, Pascal, Martin, Myriam, Bianchi, Matteo, Lundstrom, Emeli, Eloranta, Maija-Leena, Sandling, Johanna K., Sjöwall, Christopher, Jonsen, Andreas, Gunnarsson, Iva, Rantapaa-Dahlqvist, Solbritt, Bengtsson, Anders A., Leonard, Dag, Baecklund, Eva, Jonsson, Roland, Hammenfors, Daniel, Forsblad-dElia, Helena, Eriksson, Per, Mandl, Thomas, Bucher, Sara Magnusson, Norheim, Katrine B., Johnsen, Svein Joar Auglaend, Omdal, Roald, Kvarnstrom, Marika, Wahren-Herlenius, Marie, Notarnicola, Antonella, Andersson, Helena, Molberg, Oyvind, Diederichsen, Louise Pyndt, Almlof, Jonas, Syvanen, Ann-Christine, Kozyrev, Sergey V, Lindblad-Toh, Kerstin, Nilsson, Bo, Blom, Anna M., Lundberg, Ingrid E., Nordmark, Gunnel, Diaz-Gallo, Lina Marcela, Svenungsson, Elisabet, Ronnblom, Lars, Lundtoft, Christian, Pucholt, Pascal, Martin, Myriam, Bianchi, Matteo, Lundstrom, Emeli, Eloranta, Maija-Leena, Sandling, Johanna K., Sjöwall, Christopher, Jonsen, Andreas, Gunnarsson, Iva, Rantapaa-Dahlqvist, Solbritt, Bengtsson, Anders A., Leonard, Dag, Baecklund, Eva, Jonsson, Roland, Hammenfors, Daniel, Forsblad-dElia, Helena, Eriksson, Per, Mandl, Thomas, Bucher, Sara Magnusson, Norheim, Katrine B., Johnsen, Svein Joar Auglaend, Omdal, Roald, Kvarnstrom, Marika, Wahren-Herlenius, Marie, Notarnicola, Antonella, Andersson, Helena, Molberg, Oyvind, Diederichsen, Louise Pyndt, Almlof, Jonas, Syvanen, Ann-Christine, Kozyrev, Sergey V, Lindblad-Toh, Kerstin, Nilsson, Bo, Blom, Anna M., Lundberg, Ingrid E., Nordmark, Gunnel, Diaz-Gallo, Lina Marcela, Svenungsson, Elisabet, and Ronnblom, Lars

Abstract

Objective Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjogrens syndrome (SS), or myositis. Methods Using targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls. Results A prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2-33.3]), whereas a weaker association was seen in patients without SSA/SSB autoantibodies (OR 3.1 [95% CI 1.7-5.5]). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals capacity to deposit C4b on immune complexes. Conclusion We show that a low C4A copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account., Funding Agencies|Swedish Research Council for Medicine and Health; Swedish Rheumatism Association; Swedish Society of Medicine; Swedish Heart Lung Foundation; Stockholm County; Karolinska Institutet; Wallenberg Scholarship; King Gustav Vs 80-Year Foundation

Published
2022
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13. Increased CSF-decorin predicts brain pathological changes driven by Alzheimers A beta amyloidosis

Author

Jiang, Richeng, Smailovic, Una, Haytural, Hazal, Tijms, Betty M., Li, Hao, Haret, Robert Mihai, Shevchenko, Ganna, Chen, Gefei, Abelein, Axel, Gobom, Johan, Frykman, Susanne, Sekiguchi, Misaki, Fujioka, Ryo, Watamura, Naoto, Sasaguri, Hiroki, Nyström, Sofie, Hammarström, Per, Saido, Takaomi C., Jelic, Vesna, Syvanen, Stina, Zetterberg, Henrik, Winblad, Bengt, Bergquist, Jonas, Visser, Pieter Jelle, Nilsson, Per, Jiang, Richeng, Smailovic, Una, Haytural, Hazal, Tijms, Betty M., Li, Hao, Haret, Robert Mihai, Shevchenko, Ganna, Chen, Gefei, Abelein, Axel, Gobom, Johan, Frykman, Susanne, Sekiguchi, Misaki, Fujioka, Ryo, Watamura, Naoto, Sasaguri, Hiroki, Nyström, Sofie, Hammarström, Per, Saido, Takaomi C., Jelic, Vesna, Syvanen, Stina, Zetterberg, Henrik, Winblad, Bengt, Bergquist, Jonas, Visser, Pieter Jelle, and Nilsson, Per

Abstract

Cerebrospinal fluid (CSF) biomarkers play an important role in diagnosing Alzheimers disease (AD) which is characterized by amyloid-beta (A beta) amyloidosis. Here, we used two App knock-in mouse models, App(NL-F/NL-F) and App(NL-G-F/NL-G-F), exhibiting AD-like A beta pathology to analyze how the brain pathologies translate to CSF proteomes by label-free mass spectrometry (MS). This identified several extracellular matrix (ECM) proteins as significantly altered in App knock-in mice. Next, we compared mouse CSF proteomes with previously reported human CSF MS results acquired from patients across the AD spectrum. Intriguingly, the ECM protein decorin was similarly and significantly increased in both App(NL-F/NL-F) and App(NL-G-F/NL-G-F) mice, strikingly already at three months of age in the App(NL-F/NL-F) mice and preclinical AD subjects having abnormal CSF-A beta 42 but normal cognition. Notably, in this group of subjects, CSF-decorin levels positively correlated with CSF-A beta 42 levels indicating that the change in CSF-decorin is associated with early A beta amyloidosis. Importantly, receiver operating characteristic analysis revealed that CSF-decorin can predict a specific AD subtype having innate immune activation and potential choroid plexus dysfunction in the brain. Consistently, in App(NL-F/NL-F) mice, increased CSF-decorin correlated with both AP plaque load and with decorin levels in choroid plexus. In addition, a low concentration of human A beta 42 induces decorin secretion from mouse primary neurons. Interestingly, we finally identify decorin to activate neuronal autophagy through enhancing lysosomal function. Altogether, the increased CSF-decorin levels occurring at an early stage of A beta amyloidosis in the brain may reflect pathological changes in choroid plexus, present in a subtype of AD subjects., Funding Agencies|Karolinska Institute; Hallsten Research Foundation; Swedish Research Council; Swedish Brain foundation; Torsten Soderberg Foundation; Erling-Persson Family Foundation; China Scholarship Council; Swedish Research Council [2015-4870]; uropean Unions Horizon 2020 research and innovation program under the Marie Sk1odowska-Curie grant [676144]; Gun and Bertil Stohnes Foundation; Gamla Tjanarinnor grant; Margaretha af Ugglas Stiftelse; Alzheimerfonden [AF-930934]; Alzheimerfonden; Hjarnfonden; Swedish Brain Foundation [ALZ2022-0004, FO-2020-0207]; European Research Council [681712]; Swedish State Support for Clinical Research [ALFGBG-720931]; Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862]; AD Strategic Fund; Alzheimers Association [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]; Olav Thon Foundation; Stiftelsen for Gamla Tjanarinnor, Hjarnfonden, Sweden [FO2019-0228]; European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [860197]; European Union Joint Program for Neurodegenerative Disorders [JPND2021-00694]; UK Dementia Research Institute at UCL

Published
2022
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14. Comparison Between Technostress Instruments Among Education and Health Care Sectors

Author

Kimmo Vanni, Antti Syvanen, and Jarmo Viteli

Abstract

Background: Online meetings in Teams, Zoom and Google Meet have become a relevant part of daily activities in business, research and education. The Covid-19 pandemic forced employees to move from physical meetings to online meetings with very limited time to familiarize themselves with interfaces and functionalities of the applications. It has widely been reported that use of technology may stress people, and the phenomenon is known as technostress. However, the research about technostress due to online meetings and used tools has still been scarce. Objective: We aimed to measure technostress due to online meetings and its factors among university teachers and researchers, and clerical employees. We also aimed to compare which measure (dependent variable) would be the most reliable. Methods: A survey was conducted and the data were handled by SPSS-26 statistical package and AMOS. Statistical analyses were done by linear regressions, correlations, analysis of variance, and both experimental and confirmatory factor analysis. The used dependent variables of analyses were the sum variables of Cohen-4 stress measure and Salanova's technostress measure. Results: Analyses showed that increased online meeting hours due to Covid-19 pandemic has statistically significant impact on perceived technostress. The impact of user interfaces of online meeting tools on perceived technostress was the most relevant factor. Other significant factors were e.g., information security and topics of the meetings. Technostress between genders was statistically non-significant but age was a significant factor. Cohen-4 stress measure was not adequate for technostress assessments, whereas Salanova's technostress measure worked well. Conclusion: Covid-19 pandemic has had an impact on the use of online meetings tools. Even if tools have been useful and the relevant part of office work, the use of tools may affect technostress. The most relevant factor for technostress was the user interfaces. Based on the result, we recommend software companies to focus on developing user interfaces and assessing user experiences of online meeting tools.

Published
2022
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24. Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX

Author

Hom, Geoffrey, Graham, Robert R., Modrek, Barmak, Taylor, Kimberly E., Ortmann, Ward, Garnier, Sophie, Lee, Annette T., Chung, Sharon A., Ferreira, Ricardo C., Pant, P.V. Krishna, Ballinger, Dennis G., Kosoy, Roman, Demirci, F. Yesim, Kamboh, Ilyas, Kao, Amy H., Chao Tian, Gunnarsson, Iva, Bengtsson, Anders A., Rantapaa-Dahlqvist, Solbritt, Petri, Michelle, Manzi, Susan, Seldin, Michael F., Ronnblom, Lars, Syvanen, Ann-Christine, Criswell, Lindsey A., Gregersen, Peter K., and Behrens, Timothy W.

Subjects
Gene expression -- Research, Single nucleotide polymorphisms -- Research, Systemic lupus erythematosus -- Development and progression, Systemic lupus erythematosus -- Genetic aspects
Abstract

A study to ascertain if the development of systemic lupus erythematosus (SLE) is influenced by the presence of certain genes is conducted. Results confirm that the hereditary genes play a role in the development as also reduced expression of BLK and increase depression of C8orf13 and variants in the ITGAM-ITGAX region.

Published
2008

25. Contributions of de novo variants to systemic lupus erythematosus

Author

Carlsson Almlof, Jonas, Nystedt, Sara, Mechtidou, Aikaterini, Leonard, Dag, Eloranta, Maija-Leena, Grosso, Giorgia, Sjöwall, Christopher, Bengtsson, Anders A., Jonsen, Andreas, Gunnarsson, Iva, Svenungsson, Elisabet, Ronnblom, Lars, Sandling, Johanna K., Syvanen, Ann-Christine, Carlsson Almlof, Jonas, Nystedt, Sara, Mechtidou, Aikaterini, Leonard, Dag, Eloranta, Maija-Leena, Grosso, Giorgia, Sjöwall, Christopher, Bengtsson, Anders A., Jonsen, Andreas, Gunnarsson, Iva, Svenungsson, Elisabet, Ronnblom, Lars, Sandling, Johanna K., and Syvanen, Ann-Christine

Abstract

By performing whole-genome sequencing in a Swedish cohort of 71 parent-offspring trios, in which the child in each family is affected by systemic lupus erythematosus (SLE, OMIM 152700), we investigated the contribution of de novo variants to risk of SLE. We found de novo single nucleotide variants (SNVs) to be significantly enriched in gene promoters in SLE patients compared with healthy controls at a level corresponding to 26 de novo promoter SNVs more in each patient than expected. We identified 12 de novo SNVs in promoter regions of genes that have been previously implicated in SLE, or that have functions that could be of relevance to SLE. Furthermore, we detected three missense de novo SNVs, five de novo insertion-deletions, and three de novo structural variants with potential to affect the expression of genes that are relevant for SLE. Based on enrichment analysis, disease-affecting de novo SNVs are expected to occur in one-third of SLE patients. This study shows that de novo variants in promoters commonly contribute to the genetic risk of SLE. The fact that de novo SNVs in SLE were enriched to promoter regions highlights the importance of using whole-genome sequencing for identification of de novo variants., Funding Agencies|Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; Swedish Research Council for Medicine and Health [2018-02399, 2017-02000]; Swedish Rheumatism Association; King Gustaf Vs 80-year Foundation; Swedish Society of Medicine; Ingegerd Johansson donation

Published
2021
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26. Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing

Author

Sandling, Johanna K., Pucholt, Pascal, Hultin Rosenberg, Lina, Farias, Fabiana H. G., Kozyrev, Sergey V, Eloranta, Maija-Leena, Alexsson, Andrei, Bianchi, Matteo, Padyukov, Leonid, Bengtsson, Christine, Jonsson, Roland, Omdal, Roald, Lie, Benedicte A., Massarenti, Laura, Steffensen, Rudi, Jakobsen, Marianne A., Lillevang, Soren T., Lerang, Karoline, Molberg, Oyvind, Voss, Anne, Troldborg, Anne, Jacobsen, Soren, Syvanen, Ann-Christine, Jonsen, Andreas, Gunnarsson, Iva, Svenungsson, Elisabet, Rantapaa-Dahlqvist, Solbritt, Bengtsson, Anders A., Sjöwall, Christopher, Leonard, Dag, Lindblad-Toh, Kerstin, Ronnblom, Lars, Sandling, Johanna K., Pucholt, Pascal, Hultin Rosenberg, Lina, Farias, Fabiana H. G., Kozyrev, Sergey V, Eloranta, Maija-Leena, Alexsson, Andrei, Bianchi, Matteo, Padyukov, Leonid, Bengtsson, Christine, Jonsson, Roland, Omdal, Roald, Lie, Benedicte A., Massarenti, Laura, Steffensen, Rudi, Jakobsen, Marianne A., Lillevang, Soren T., Lerang, Karoline, Molberg, Oyvind, Voss, Anne, Troldborg, Anne, Jacobsen, Soren, Syvanen, Ann-Christine, Jonsen, Andreas, Gunnarsson, Iva, Svenungsson, Elisabet, Rantapaa-Dahlqvist, Solbritt, Bengtsson, Anders A., Sjöwall, Christopher, Leonard, Dag, Lindblad-Toh, Kerstin, and Ronnblom, Lars

Abstract

Objectives Systemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE. Methods We undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS). Results We identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes. Conclusions Our results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection., Funding Agencies|AstraZeneca-Science for Life Laboratory Research Collaboration grant (DISSECT); Swedish Research Council for Medicine and Health [2018-02399, 2018-02535]; Swedish Rheumatism Association; King Gustav Vs 80-year Foundation; Swedish-Heart-Lung foundationSwedish Heart-Lung Foundation; Wallenberg Scholar Award; Swedish Society of Medicine; Science for Life Laboratory; Swedish Research Council (VR-RFI)Swedish Research Council; Uppsala University; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation

Published
2021
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27. Three functional variants of IFN regulatory factor 5 (IRFS) define risk and protective haplotypes for human lupus

Author

Graham, Robert R., Kyogoku, Chieko, Sigurdsson, Snaevar, Vlasova, Irina A., Davies, Leela R.L., Baechler, Emily C., Plenge, Robert M., Koeuth, Thearith, Ortmann, Ward A., Hom, Geoffrey, Bauer, Jason W., Gillett, Clarence, Burtt, Noel, Graham, Deborah S. Cunninghame, Onofrio, Robert, Petri, Michelle, Gunnarsson, Iva, Svenungsson, Elisabet, Ronnblom, Lars, Nordmark, Gunnel, Gregersen, Peter K., Moser, Kathy, Gaffney, Patrick M., Criswell, Lindsey A., Vyse, Timothy J., Syvanen, Ann-Christine, Bohjanen, Paul R., Daly, Mark J., Behrens, Timothy W., and Altshuler, David

Subjects
Haplotypes -- Research, Interferon -- Research, Systemic lupus erythematosus -- Research, Science and technology
Abstract

Systematic genome-wide studies to map genomic regions associated with human diseases are becoming more practical. Increasingly, efforts will be focused on the identification of the specific functional variants responsible for the disease. The challenges of identifying causal variants include the need for complete ascertainment of genetic variants and the need to consider the possibility of multiple causal alleles. We recently reported that risk of systemic lupus erythematosus (SLE) is strongly associated with a common SNP in IFN regulatory factor 5 (IRF5), and that this variant altered spicing in a way that might provide a functional explanation for the reproducible association to SLE risk. Here, by resequencing and genotyping in patients with SLE, we find evidence for three functional alleles of IRF5: the previously described exon 1B splice site variant, a 30-bp in-frame insertion/deletion variant of exon 6 that alters a proline-, glutamic acid-, serine- and threonine-rich domain region, and a variant in a conserved polyA+ signal sequence that alters the length of the 3' UTR and stability of IRF5 mRNAs. Haplotypes of these three variants define at least three distinct levels of risk to SLE. Understanding how combinations of variants influence IRF5 function may offer etiological and therapeutic insights in SLE; more generally, IRF5 and SLE illustrates how multiple common variants of the same gene can together influence risk of common disease. interferon pathway | systemic lupus erythematosus

Published
2007

28. Genetic variation in putative regulatory loci controlling gene expression in breast cancer

Author

Kristensen, Vessela N., Edvardsen, Hege, Tsalenko, Anya, Nordgard, Silje H., Sorlie, Therese, Sharan, Roded, Vailaya, Aditya, Ben-Dor, Amir, Lonning, Per Eystein, Lien, Sigbjorn, Omholt, Stigbjorn, Syvanen, Ann-Christine, Yakhini, Zohar, and Borresen-Dale, Anne-Lise

Subjects
Breast cancer -- Research, Genetics -- Research, Science and technology
Abstract

Candidate singie-nucleotide polymorphisms (SNPs) were analyzed for associations to an unselected whole genome pool of tumor mRNA transcripts in 50 unrelated patients with breast cancer. SNPs were selected from 203 candidate genes of the reactive oxygen species pathway. We describe a general statistical framework for the simultaneous analysis of gene expression data and SNP genotype data measured for the same cohort, which revealed significant associations between subsets of SNPs and transcripts, shedding light on the underlying biology. We identified SNPs in EGF, IL1A, MAPK8, XPC, SOD2, and ALOX12 that are associated with the expression patterns of a significant number of transcripts, indicating the presence of regulatory SNPs in these genes. SNPs were found to act in trans in a total of 115 genes. SNPs in 43 of these 115 genes were found to act both in cis and in trans. Finally, subsets of SNPs that share significantly many common associations with a set of transcripts (biclusters) were identified. The subsets of transcripts that are significantly associated with the same set of SNPs or to a single SNP were shown to be functionally coherent in Gene Ontology and pathway analyses and coexpressed in other independent data sets, suggesting that many of the observed associations are within the same functional pathways. To our knowledge, this article is the first study to correlate SNP genotype data in the germ line with somatic gene expression data in breast tumors. It provides the statistical framework for further genotype expression correlation studies in cancer data sets. genotype-phenotype interaction | locus control region | single-nucleotide polymorphism expression association

Published
2006

29. Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus

Author

Sigurdsson, Snaevar, Nordmark, Gunnel, Goring, Harald H.H., Lindroos, Katarina, Wiman, Ann-Christin, Sturfelt, Gunnar, Jonsen, Andreas, Rantapaa-Dahlqvist, Solbritt, Moller, Bozena, Kere, Juha, Koskenmies, Sari, Widen, Elisabeth, Eloranta, Maija-Leena, Julkunen, Heikki, Kristjansdottir, Helga, Steinsson, Kristjan, Alm, Gunnar, Ronnblom, Lars, and Syvanen, Ann-Christine

Subjects
Lupus erythematosus -- Research, Biological sciences
Published
2005

32. Unexpectedly high allelic diversity at the KIT locus causing dominant white color in the domestic pig

Author

Pielberg, G., Olsson, C., Syvanen, A.-C., and Andersson, L.

Subjects
Genetic research -- Analysis, Color of animals -- Genetic aspects, Gene mutations -- Physiological aspects, Cells -- Growth, Phenotype -- Genetic aspects, Biological sciences
Abstract

Mutations in KIT encoding the mast/stem cell growth factor receptor (MGF) are responsible for coat color variation in domestic pigs. The dominant white phenotype is caused by two mutations, a gene duplication and a splice mutation in one of the copies leading to skipping of exon 17. Here we applied minisequencing and pyrosequencing for quantitative analysis of the number of copies with the splice form. An unexpectedly high genetic diversity was revealed in white pigs. We found four different KIT alleles in a small sample of eight Large White females used as founder animals in a wild boar intercross. A similar number of KIT alleles was found in commercial populations of white Landrace and Large White pigs. We provide evidence for at least two new KIT alleles in pigs, both with a triplication of the gene. The results imply that KIT alleles with the duplication are genetically unstable and new alleles are most likely generated by unequal crossing over. This study provides an improved method for genotyping the complicated Dominant white/KIT locus in pigs. The results also suggest that some alleles may be associated with negative pleiotropic effects on other traits.

Published
2002

35. Recurrence of Marfan syndrome as a result of parental germ-line mosaicism for an FBN1 mutation

Author

Rantamaki, Terhi, Kaitila, Ilkka, Syvanen, Ann-Christine, Lukka, Matti, and Peltonen, Leena

Subjects
Marfan syndrome -- Research, Connective tissue diseases -- Research, Genetic disorders -- Research, Biological sciences
Abstract

Studies support a link between Marfan syndrome and parental genetic origin. This connective tissue disorder has been identified through genotyping, but required sensitive and quantitative solid-phase minisequencing to eliminate possible carrier locations. Since the mutation could not be identified in a paternal sperm sample, the mosaicism may be maternal in origin.

Published
1999

36. Genome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse

Author

Wade, C. M., Giulotto, E., Sigurdsson, S., Zoti, M., Gnerre, S., Imsland, F., Lear, T. L., Adelson, D. L., Bailey, E., Bellone, R. R., Blocker, H., Distl, O., Edgar, R. C., Garber, M., Leeb, T., Mauceli, E., MacLeod, J. N., T. Penedo, M. C., Raison, J. M., Sharpe, T., Vogel, J., Andersson, L., Antczak, D. F., Biagi, T., Binns, M. M., Chowdhary, B. P., Coleman, S. J., Valle, Delia G., Fryc, S., Guérin, G., Hasegawa, T., Hill, E. W., Jurka, J., Kiialainen, A., Lindgren, G., Liu, J., Magnani, E., Mickelson, J. R., Murray, J., Nergadze, S. G., Onofrio, R., Pedroni, S., Piras, M. F., Raudsepp, T., Rocchi, M., Reed, K. H., Ryder, O. A., Searle, S., Skow, L., Swinburne, J. E., Syvanen, A. C., Tozaki, T., Valberg, S. J., Vaudin, M., White, J. R., Zody, M. C., Lander, E. S., and Lindblad-Toh, K.

Published
2009

37. Variation in STAT4 is associated with systemic lupus erythematosus in a Finnish family cohort

Author

Hellquist, Anna, Sandling, Johanna K., Zucchelli, Marco, Koskenmies, Sari, Julkunen, Heikki, D'Amato, Mauro, Garnier, Sophie, Syvanen, Ann-Christine, and Kere, Juha

Subjects
Systemic lupus erythematosus -- Genetic aspects, Systemic lupus erythematosus -- Risk factors, Systemic lupus erythematosus -- Demographic aspects, Systemic lupus erythematosus -- Research, STAT proteins -- Genetic aspects, STAT proteins -- Physiological aspects, STAT proteins -- Research, Genetic variation -- Research, Health
Published
2010

38. A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus

Author

Svenungsson, Elisabet, Gustafsson, Johanna, Leonard, Dag, Sandling, Johanna, Gunnarsson, Iva, Nordmark, Gunnel, Jonsen, Andreas, Bengtsson, Anders A., Sturfelt, Gunnar, Rantapaa-Dahlqvist, Solbritt, Elvin, Kerstin, Sundin, Ulf, Garnier, Sophie, Simard, Julia F., Sigurdsson, Snaevar, Padyukov, Leonid, Syvanen, Ann-Christine, and Ronnblom, Lars

Subjects
Systemic lupus erythematosus -- Risk factors, Systemic lupus erythematosus -- Genetic aspects, Systemic lupus erythematosus -- Research, Cerebrovascular disease -- Risk factors, Cerebrovascular disease -- Genetic aspects, Cerebrovascular disease -- Research, Antiphospholipid antibodies -- Genetic aspects, Antiphospholipid antibodies -- Research, STAT proteins -- Genetic aspects, STAT proteins -- Research, Health
Published
2010

43. Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations

Author

Kristjansdottir, G., Sandling, J.K., Bonetti, A., Roos, I.M., Milani, L., Wang, C., Gustafsdottir, S.M., Sigurdsson, S., Lundmark, A., Tienari, P.J., Koivisto, K., Elovaara, I., Pirttila, T., Reunanen, M., Peltonen, L., Saarela, J., Hillert, J., Olsson, T., Landegren, U., Alcina, A., Fernandez, O., Leyva, L., Guerrero, M., Lucas, M., Izquierdo, G., Matesanz, F., and Syvanen, A.-C.

Subjects
Interferon -- Genetic aspects, Genetic variation -- Analysis, Multiple sclerosis -- Development and progression, Multiple sclerosis -- Genetic aspects, Multiple sclerosis -- Demographic aspects, Multiple sclerosis -- Research, Health
Published
2008

44. Quality control and conduct of genome-wide association meta-analyses

Author

Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis GR, Absher D, Alavere H, Albrecht E, Allen HL, Almgren P, Amin N, Amouyel P, Anderson D, Arnold AM, Arveiler D, Aspelund T, Asselbergs FW, Assimes TL, Atalay M, Attwood AP, Atwood LD, Bakker SJ, Balkau B, Balmforth AJ, Barlassina C, Barroso I, Basart H, Bauer S, Beckmann JS, Beilby JP, Bennett AJ, Ben Shlomo Y, Bergman RN, Bergmann S, Berndt SI, Biffar R, Di Blasio AM, Boehm BO, Boehnke M, Boeing H, Boerwinkle E, Bolton JL, Bonnefond A, Bonnycastle LL, Boomsma DI, Borecki IB, Bornstein SR, Bouatia Naji N, Boucher G, Bragg Gresham JL, BRAMBILLA, PAOLO, Bruinenberg M, Buchanan TA, Buechler C, Cadby G, Campbell H, Caulfield MJ, Cavalcanti Proença C, CESANA, GIANCARLO, Chanock SJ, Chasman DI, Chen YD, Chines PS, Clegg DJ, Coin L, Collins FS, Connell JM, Cookson W, Cooper MN, Croteau Chonka DC, Cupples LA, Cusi D, Day FR, Day IN, Dedoussis GV, Dei M, Deloukas P, Dermitzakis ET, Dimas AS, Dimitriou M, Dixon AL, Dörr M, van Duijn CM, Ebrahim S, Edkins S, Eiriksdottir G, Eisinger K, Eklund N, Elliott P, Erbel R, Erdmann J, Erdos MR, Eriksson JG, Esko T, Estrada K, Evans DM, de Faire U, Fall T, Farrall M, Feitosa MF, Ferrario MM, Ferreira T, Ferrières J, Fischer K, Fisher E, Fowkes G, Fox CS, Franke L, Franks PW, Fraser RM, Frau F, Frayling T, Freimer NB, Froguel P, Fu M, Gaget S, Ganna A, Gejman PV, Gentilini D, Geus EJ, Gieger C, Gigante B, Gjesing AP, Glazer NL, Goddard ME, Goel A, Grallert H, Gräßler J, Grönberg H, Groop LC, Groves CJ, Gudnason V, Guiducci C, Gustafsson S, Gyllensten U, Hall AS, Hall P, Hallmans G, Hamsten A, Hansen T, Haritunians T, Harris TB, van der Harst P, Hartikainen AL, Hassanali N, Hattersley AT, Havulinna AS, Hayward C, Heard Costa NL, Heath AC, Hebebrand J, Heid IM, den Heijer M, Hengstenberg C, Herzig KH, Hicks AA, Hingorani A, Hinney A, Hirschhorn JN, Hofman A, Holmes CC, Homuth G, Hottenga JJ, Hovingh KG, Hu FB, Hu YJ, Huffman JE, Hui J, Huikuri H, Humphries SE, Hung J, Hunt SE, Hunter D, Hveem K, Hyppönen E, Igl W, Illig T, Ingelsson E, Iribarren C, Isomaa B, Jackson AU, Jacobs KB, James AL, Jansson JO, Jarick I, Jarvelin MR, Jöckel KH, Johansson Å, Johnson T, Jolley J, Jørgensen T, Jousilahti P, Jula A, Justice AE, Kaakinen M, Kähönen M, Kajantie E, Kanoni S, Kao WH, Kaplan LM, Kaplan RC, Kaprio J, Kapur K, Karpe F, Kathiresan S, Kee F, Keinanen Kiukaanniemi SM, Ketkar S, Kettunen J, Khaw KT, Kiemeney LA, Kilpeläinen TO, Kinnunen L, Kivimaki M, Kivmaki M, Van der Klauw MM, Kleber ME, Knowles JW, Koenig W, Kolcic I, Kolovou G, König IR, Koskinen S, Kovacs P, Kraft P, Kraja AT, Kristiansson K, KrjutÅjkov K, Kroemer HK, Krohn JP, Krzelj V, Kuh D, Kulzer JR, Kumari M, Kutalik Z, Kuulasmaa K, Kuusisto J, Kvaloy K, Laakso M, Laitinen JH, Lakka TA, Lamina C, Langenberg C, Lantieri O, Lathrop GM, Launer LJ, Lawlor DA, Lawrence RW, Leach IM, Lecoeur C, Lee SH, Lehtimäki T, Leitzmann MF, Lettre G, Levinson DF, Li G, Li S, Liang L, Lin DY, Lind L, Lindgren CM, Lindström J, Liu J, Liuzzi A, Locke AE, Lokki ML, Loley C, Loos RJ, Lorentzon M, Luan J, Luben RN, Ludwig B, Madden PA, Mägi R, Magnusson PK, Mangino M, Manunta P, Marek D, Marre M, Martin NG, März W, Maschio A, Mathieson I, McArdle WL, McCaroll SA, McCarthy A, McCarthy MI, McKnight B, Medina Gomez C, Medland SE, Meitinger T, Metspalu A, van Meurs JB, Meyre D, Midthjell K, Mihailov E, Milani L, Min JL, Moebus S, Moffatt MF, Mohlke KL, Molony C, Monda KL, Montgomery GW, Mooser V, Morken MA, Morris AD, Morris AP, Mühleisen TW, Müller Nurasyid M, Munroe PB, Musk AW, Narisu N, Navis G, Neale BM, Nelis M, Nemesh J, Neville MJ, Ngwa JS, Nicholson G, Nieminen MS, Njølstad I, Nohr EA, Nolte IM, North KE, Nöthen MM, Nyholt DR, O'Connell JR, Ohlsson C, Oldehinkel AJ, van Ommen GJ, Ong KK, Oostra BA, Ouwehand WH, Palmer CN, Palmer LJ, Palotie A, Paré G, Parker AN, Paternoster L, Pawitan Y, Pechlivanis S, Peden JF, Pedersen NL, Pedersen O, Pellikka N, Peltonen L, Penninx B, Perola M, Perry JR, Person T, Peters A, Peters MJ, Pichler I, Pietiläinen KH, Platou CG, Polasek O, Pouta A, Power C, Pramstaller PP, Preuss M, Price JF, Prokopenko I, Province MA, Psaty BM, Purcell S, Pütter C, Qi L, Quertermous T, Radhakrishnan A, Raitakari O, Randall JC, Rauramaa R, Rayner NW, Rehnberg E, Rendon A, Ridderstråle M, Ridker PM, Ripatti S, Rissanen A, Rivadeneira F, Rivolta C, Robertson NR, Rose LM, Rudan I, Saaristo TE, Sager H, Salomaa V, Samani NJ, Sambrook JG, Sanders AR, Sandholt C, Sanna S, Saramies J, Schadt EE, Scherag A, Schipf S, Schlessinger D, Schreiber S, Schunkert H, Schwarz PE, Scott LJ, Shi J, Shin SY, Shuldiner AR, Shungin D, Signorini S, Silander K, Sinisalo J, Skrobek B, Smit JH, Smith AV, Smith GD, Snieder H, Soranzo N, Sørensen TI, Sovio U, Spector TD, Speliotes EK, Stančáková A, Stark K, Stefansson K, Steinthorsdottir V, Stephens JC, Stirrups K, Stolk RP, Strachan DP, Strawbridge RJ, Stringham HM, Stumvoll M, Surakka I, Swift AJ, Syvanen AC, Tammesoo ML, Teder Laving M, Teslovich TM, Teumer A, Theodoraki EV, Thomson B, Thorand B, Thorleifsson G, Thorsteinsdottir U, Timpson NJ, Tönjes A, Tregouet DA, Tremoli E, Trip MD, Tuomi T, Tuomilehto J, Tyrer J, Uda M, Uitterlinden AG, Usala G, Uusitupa M, Valle TT, Vandenput L, Vatin V, Vedantam S, de Vegt F, Vermeulen SH, Viikari J, Virtamo J, Visscher PM, Vitart V, Van Vliet Ostaptchouk JV, Voight BF, Vollenweider P, Volpato CB, Völzke H, Waeber G, Waite LL, Wallaschofski H, Walters GB, Wang Z, Wareham NJ, Watanabe RM, Watkins H, Weedon MN, Welch R, Weyant RJ, Wheeler E, White CC, Wichmann HE, Widen E, Wild SH, Willemsen G, Willer CJ, Wilsgaard T, Wilson JF, van Wingerden S, Winkelmann BR, Winkler TW, Witte DR, Witteman JC, Wolffenbuttel BH, Wong A, Wood AR, Workalemahu T, Wright AF, Yang J, Yarnell JW, Zgaga L, Zhao JH, Zillikens MC, Zitting P, Zondervan KT, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis, G, Absher, D, Alavere, H, Albrecht, E, Allen, H, Almgren, P, Amin, N, Amouyel, P, Anderson, D, Arnold, A, Arveiler, D, Aspelund, T, Asselbergs, F, Assimes, T, Atalay, M, Attwood, A, Atwood, L, Bakker, S, Balkau, B, Balmforth, A, Barlassina, C, Barroso, I, Basart, H, Bauer, S, Beckmann, J, Beilby, J, Bennett, A, Ben Shlomo, Y, Bergman, R, Bergmann, S, Berndt, S, Biffar, R, Di Blasio, A, Boehm, B, Boehnke, M, Boeing, H, Boerwinkle, E, Bolton, J, Bonnefond, A, Bonnycastle, L, Boomsma, D, Borecki, I, Bornstein, S, Bouatia Naji, N, Boucher, G, Bragg Gresham, J, Brambilla, P, Bruinenberg, M, Buchanan, T, Buechler, C, Cadby, G, Campbell, H, Caulfield, M, Cavalcanti Proença, C, Cesana, G, Chanock, S, Chasman, D, Chen, Y, Chines, P, Clegg, D, Coin, L, Collins, F, Connell, J, Cookson, W, Cooper, M, Cupples, L, Cusi, D, Day, I, Dedoussis, G, Dei, M, Deloukas, P, Dermitzakis, E, Dimas, A, Dimitriou, M, Dixon, A, Dörr, M, van Duijn, C, Ebrahim, S, Edkins, S, Eiriksdottir, G, Eisinger, K, Eklund, N, Elliott, P, Erbel, R, Erdmann, J, Erdos, M, Eriksson, J, Estrada, K, Evans, D, de Faire, U, Farrall, M, Feitosa, M, Ferrario, M, Ferrières, J, Fischer, K, Fisher, E, Fowkes, G, Fox, C, Franke, L, Franks, P, Fraser, R, Frau, F, Frayling, T, Freimer, N, Froguel, P, Fu, M, Gaget, S, Ganna, A, Gejman, P, Gentilini, D, Geus, E, Gieger, C, Gigante, B, Gjesing, A, Glazer, N, Goddard, M, Goel, A, Grallert, H, Gräßler, J, Grönberg, H, Groop, L, Groves, C, Gudnason, V, Guiducci, C, Gyllensten, U, Hall, A, Hall, P, Hallmans, G, Hamsten, A, Hansen, T, Haritunians, T, Harris, T, van der Harst, P, Hartikainen, A, Hassanali, N, Hattersley, A, Havulinna, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, den Heijer, M, Hengstenberg, C, Herzig, K, Hicks, A, Hingorani, A, Hinney, A, Hirschhorn, J, Hofman, A, Holmes, C, Homuth, G, Hottenga, J, Hovingh, K, Hu, F, Hu, Y, Huffman, J, Hui, J, Huikuri, H, Humphries, S, Hung, J, Hunt, S, Hunter, D, Hveem, K, Hyppönen, E, Igl, W, Illig, T, Ingelsson, E, Iribarren, C, Isomaa, B, Jackson, A, Jacobs, K, James, A, Jansson, J, Jarick, I, Jarvelin, M, Jöckel, K, Johansson, Å, Johnson, T, Jolley, J, Jørgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kähönen, M, Kajantie, E, Kanoni, S, Kao, W, Kaplan, L, Kaplan, R, Kaprio, J, Kapur, K, Karpe, F, Kathiresan, S, Kee, F, Keinanen Kiukaanniemi, S, Ketkar, S, Kettunen, J, Khaw, K, Kiemeney, L, Kinnunen, L, Kivimaki, M, Kivmaki, M, Van der Klauw, M, Kleber, M, Knowles, J, Koenig, W, Kolcic, I, Kolovou, G, König, I, Koskinen, S, Kovacs, P, Kraft, P, Kraja, A, Kristiansson, K, Krjutåjkov, K, Kroemer, H, Krohn, J, Krzelj, V, Kuh, D, Kulzer, J, Kumari, M, Kuulasmaa, K, Kuusisto, J, Kvaloy, K, Laakso, M, Laitinen, J, Lakka, T, Lamina, C, Langenberg, C, Lantieri, O, Lathrop, G, Launer, L, Lawlor, D, Lawrence, R, Leach, I, Lecoeur, C, Lee, S, Lehtimäki, T, Leitzmann, M, Lettre, G, Levinson, D, Li, G, Li, S, Liang, L, Lin, D, Lind, L, Lindgren, C, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Loley, C, Lorentzon, M, Luben, R, Ludwig, B, Madden, P, Magnusson, P, Mangino, M, Manunta, P, Marek, D, Marre, M, Martin, N, März, W, Maschio, A, Mathieson, I, Mcardle, W, Mccaroll, S, Mccarthy, A, Mccarthy, M, Mcknight, B, Medina Gomez, C, Medland, S, Meitinger, T, Metspalu, A, van Meurs, J, Meyre, D, Midthjell, K, Mihailov, E, Milani, L, Min, J, Moebus, S, Moffatt, M, Mohlke, K, Molony, C, Monda, K, Montgomery, G, Mooser, V, Morken, M, Morris, A, Mühleisen, T, Müller Nurasyid, M, Munroe, P, Musk, A, Narisu, N, Navis, G, Neale, B, Nelis, M, Nemesh, J, Neville, M, Ngwa, J, Nicholson, G, Nieminen, M, Njølstad, I, Nohr, E, Nolte, I, North, K, Nöthen, M, Nyholt, D, O'Connell, J, Ohlsson, C, Oldehinkel, A, van Ommen, G, Ong, K, Oostra, B, Ouwehand, W, Palmer, C, Palmer, L, Palotie, A, Paré, G, Parker, A, Paternoster, L, Pawitan, Y, Pechlivanis, S, Peden, J, Pedersen, N, Pedersen, O, Pellikka, N, Peltonen, L, Penninx, B, Perola, M, Perry, J, Person, T, Peters, A, Peters, M, Pichler, I, Pietiläinen, K, Platou, C, Polasek, O, Pouta, A, Power, C, Pramstaller, P, Preuss, M, Price, J, Prokopenko, I, Province, M, Psaty, B, Purcell, S, Pütter, C, Qi, L, Quertermous, T, Radhakrishnan, A, Raitakari, O, Rauramaa, R, Rayner, N, Rehnberg, E, Rendon, A, Ridderstråle, M, Ridker, P, Ripatti, S, Rissanen, A, Rivadeneira, F, Rivolta, C, Robertson, N, Rose, L, Rudan, I, Saaristo, T, Sager, H, Salomaa, V, Samani, N, Sambrook, J, Sanders, A, Sandholt, C, Sanna, S, Saramies, J, Schadt, E, Schipf, S, Schlessinger, D, Schreiber, S, Schunkert, H, Schwarz, P, Scott, L, Shi, J, Shin, S, Shuldiner, A, Shungin, D, Signorini, S, Silander, K, Sinisalo, J, Skrobek, B, Smit, J, Smith, A, Smith, G, Snieder, H, Soranzo, N, Sørensen, T, Sovio, U, Spector, T, Speliotes, E, Stančáková, A, Stark, K, Stefansson, K, Steinthorsdottir, V, Stephens, J, Stirrups, K, Stolk, R, Strachan, D, Strawbridge, R, Stringham, H, Stumvoll, M, Surakka, I, Swift, A, Syvanen, A, Tammesoo, M, Teder Laving, M, Teslovich, T, Teumer, A, Theodoraki, E, Thomson, B, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Timpson, N, Tönjes, A, Tregouet, D, Tremoli, E, Trip, M, Tuomi, T, Tuomilehto, J, Tyrer, J, Uda, M, Uitterlinden, A, Usala, G, Uusitupa, M, Valle, T, Vandenput, L, Vatin, V, de Vegt, F, Vermeulen, S, Viikari, J, Virtamo, J, Visscher, P, Vitart, V, Van Vliet Ostaptchouk, J, Voight, B, Vollenweider, P, Volpato, C, Völzke, H, Waeber, G, Waite, L, Wallaschofski, H, Walters, G, Wang, Z, Wareham, N, Watanabe, R, Watkins, H, Weedon, M, Welch, R, Weyant, R, Wheeler, E, White, C, Wichmann, H, Widen, E, Wild, S, Willemsen, G, Willer, C, Wilsgaard, T, Wilson, J, van Wingerden, S, Winkelmann, B, Witte, D, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Yang, J, Yarnell, J, Zgaga, L, Zhao, J, Zillikens, M, Zitting, P, Zondervan, K, Psychiatry, EMGO - Mental health, Plastic, Reconstructive and Hand Surgery, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiology, Biological Psychology, EMGO+ - Mental Health, Genetic Investigation of Anthropometric Traits (GIANT) Consortium, Abecasis, GR., Absher, D., Alavere, H., Albrecht, E., Allen, HL., Almgren, P., Amin, N., Amouyel, P., Anderson, D., Arnold, AM., Arveiler, D., Aspelund, T., Asselbergs, FW., Assimes, TL., Atalay, M., Attwood, AP., Atwood, LD., Bakker, SJ., Balkau, B., Balmforth, AJ., Barlassina, C., Barroso£££Inês£££ I., Basart, H., Bauer, S., Beckmann, JS., Beilby, JP., Bennett, AJ., Ben-Shlomo, Y., Bergman, RN., Bergmann, S., Berndt, SI., Biffar, R., Di Blasio AM., Boehm, BO., Boehnke, M., Boeing, H., Boerwinkle, E., Bolton, JL., Bonnefond, A., Bonnycastle, LL., Boomsma, DI., Borecki, IB., Bornstein, SR., Bouatia-Naji, N., Boucher, G., Bragg-Gresham, JL., Brambilla, P., Bruinenberg, M., Buchanan, TA., Buechler, C., Cadby, G., Campbell, H., Caulfield, MJ., Cavalcanti-Proença, C., Cesana, G., Chanock, SJ., Chasman, DI., Chen, YD., Chines, PS., Clegg, DJ., Coin, L., Collins, FS., Connell, JM., Cookson, W., Cooper, MN., Croteau-Chonka, DC., Cupples, LA., Cusi, D., Day, FR., Day, IN., Dedoussis, GV., Dei, M., Deloukas, P., Dermitzakis, ET., Dimas, AS., Dimitriou, M., Dixon, AL., Dörr, M., van Duijn CM., Ebrahim, S., Edkins, S., Eiriksdottir, G., Eisinger, K., Eklund, N., Elliott, P., Erbel, R., Erdmann, J., Erdos, MR., Eriksson, JG., Esko£££Tõnu£££ T., Estrada, K., Evans, DM., de Faire, U., Fall, T., Farrall, M., Feitosa, MF., Ferrario, MM., Ferreira, T., Ferrières, J., Fischer, K., Fisher, E., Fowkes, G., Fox, CS., Franke, L., Franks, PW., Fraser, RM., Frau, F., Frayling, T., Freimer, NB., Froguel, P., Fu, M., Gaget, S., Ganna, A., Gejman, PV., Gentilini, D., Geus, EJ., Gieger, C., Gigante, B., Gjesing, AP., Glazer, NL., Goddard, ME., Goel, A., Grallert, H., Gräßler, J., Grönberg, H., Groop, LC., Groves, CJ., Gudnason, V., Guiducci, C., Gustafsson, S., Gyllensten, U., Hall, AS., Hall, P., Hallmans, G., Hamsten, A., Hansen, T., Haritunians, T., Harris, TB., van der Harst, P., Hartikainen, AL., Hassanali, N., Hattersley, AT., Havulinna, AS., Hayward, C., Heard-Costa, NL., Heath, AC., Hebebrand, J., Heid, IM., den Heijer, M., Hengstenberg, C., Herzig, KH., Hicks, AA., Hingorani, A., Hinney, A., Hirschhorn, JN., Hofman, A., Holmes, CC., Homuth, G., Hottenga, JJ., Hovingh, KG., Hu, FB., Hu, YJ., Huffman, JE., Hui, J., Huikuri, H., Humphries, SE., Hung, J., Hunt, SE., Hunter, D., Hveem, K., Hyppönen, E., Igl, W., Illig, T., Ingelsson, E., Iribarren, C., Isomaa, B., Jackson, AU., Jacobs, KB., James, AL., Jansson, JO., Jarick, I., Jarvelin, MR., Jöckel, KH., Johansson£££Åsa£££ Å., Johnson, T., 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Subjects
Quality Control, Netherlands Twin Register (NTR), BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, media_common.quotation_subject, quality control, GWAMAS, Control (management), Medizin, Genome-wide association study, Biology, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Software, SDG 17 - Partnerships for the Goals, Meta-Analysis as Topic, Comparable size, Quality (business), 030304 developmental biology, media_common, Protocol (science), 0303 health sciences, business.industry, Software package, Data science, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Genome-Wide Association Study/methods, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], quality control, genome-wide association meta-analyses, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Item does not contain fulltext Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.

Published
2014
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49. The major sigma factor (RpoD) from Helicobacter pylori and other gram-negative bacteria shows an enhanced rate of divergence

Author

Solnick, Jay V., Hansen, Lori M., and Syvanen, Michael

Subjects
Helicobacter pylori -- Genetic aspects, Gram-negative bacteria -- Genetic aspects, Bacterial genetics -- Research, Biological sciences
Abstract

A research study was conducted to show the rate of evolution of Helicobacter pylori major sigma factor (H pylori RpoD) and other gram-negative bacteria's RpoD compared to gram-positive bacteria. The method used was the analysis of nucleotide sequences. The results showed that the sequence analysis of the H pylori and other gram-negative bacteria RpoD was highly divergent compared to gram-positve bacteria's RpoD.

Published
1997

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