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The STK33-Linked SNP rs4929949 Is Associated with Obesity and BMI in Two Independent Cohorts of Swedish and Greek Children  [PDF]
Mathias Rask-Andersen, George Moschonis, George P. Chrousos, Claude Marcus, George V. Dedoussis, Robert Fredriksson, Helgi B. Schi?th
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0071353
Abstract: Recent genome wide association studies (GWAS) have identified a locus on chromosome 11p15.5, closely associated with serine/threonine kinase 33 (STK33), to be associated with body mass. STK33, a relatively understudied protein, has been linked to KRAS mutation-driven cancers and explored as a potential antineoplastic drug target. The strongest association with body mass observed at this loci in GWAS was rs4929949, a single nucleotide polymorphism located within intron 1 of the gene encoding STK33. The functional implications of rs4929949 or related variants have not been explored as of yet. We have genotyped rs4929949 in two cohorts, an obesity case-control cohort of 991 Swedish children, and a cross-sectional cohort of 2308 Greek school children. We found that the minor allele of rs4929949 was associated with obesity in the cohort of Swedish children and adolescents (OR = 1.199 (95%CI: 1.002–1.434), p = 0.047), and with body mass in the cross-sectional cohort of Greek children (β = 0.08147 (95% CI: 0.1345–0.1618), p = 0.021). We observe the effects of rs4929949 on body mass to be detectable already at adolescence. Subsequent analysis did not detect any association of rs4929949 to phenotypic measurements describing body adiposity or to metabolic factors such as insulin levels, triglycerides and insulin resistance (HOMA).
The common FTO variant rs9939609 is not associated with BMI in a longitudinal study on a cohort of Swedish men born 1920-1924
Josefin A Jacobsson, Ulf Risérus, Tomas Axelsson, Lars Lannfelt, Helgi B Schi?th, Robert Fredriksson
BMC Medical Genetics , 2009, DOI: 10.1186/1471-2350-10-131
Abstract: The FTO rs9936609 was genotyped using an Illumina golden gate assay. BMI was calculated using standard methods and body fat was estimated by measuring skinfold thickness using a Harpenden caliper. Physical activity was assessed using a four question medical questionnaire.FTO rs9939609 was genotyped in 1153 elderly Swedish men taking part of a population-based cohort study, the ULSAM cohort. The risk of obesity and differences in BMI according to genotype at the ages of 50, 60, 70, 77 and 82 were investigated. We found no increased risk of obesity and no association with BMI at any age with the FTO rs9939609 variant. We found however interaction between physical activity at the age of 50 years and genotype on BMI levels (p = 0.039) and there was a clear trend towards larger BMI differences between the TT and AA carriers as well as between AT and AA carriers in the less physically active subjects.Here we found that the well established obesity risk allele for a common variant in FTO does not associate with increased BMI levels in a Swedish population of adult men which reached adulthood before the appearance of today's obesogenic enviroment. There is an interaction between physical activity and the effect of the FTO genotype on BMI levels suggesting that lack of physical activity is a requirement for an association of FTO gene variants to obesity.Today, about one in three adult can be classified as obese based on objectively measured weight and height. The increase started after the World War II, escalated in the seventies and the obesity rates have roughly tripled in the past 20 years. In Sweden one in hundred is considered morbidly obese today compared to one in thousand in the early 1970s [1-4].This worldwide rapid increase in the prevalence of obesity is much due to environmental factors, such as a sedentary lifestyle and develops from an imbalance between energy ingested and expended [5]. It is however also widely accepted that obesity is under strong genetic con
Associations of ECP (eosinophil cationic protein)-gene polymorphisms to allergy, asthma, smoke habits and lung function in two Estonian and Swedish sub cohorts of the ECRHS II study
Ulla-Britt J?nsson, Lena H?kansson, Rain J?gi, Christer Janson, Per Venge
BMC Pulmonary Medicine , 2010, DOI: 10.1186/1471-2466-10-36
Abstract: Swedish and Estonian subjects (n = 757) were selected from the larger cohort of the ECRHS II study cohort. The prevalence of the gene polymorphisms ECP434(G>C) (rs2073342), ECP562(G>C) (rs2233860) and ECP c.-38(A>C) (rs2233859) were analysed by DNA sequencing and/or real-time PCR and related to questionnaire-based information of allergy, asthma, smoking habits and to lung functions.Genotype prevalence showed both ethnic and gender differences. Close associations were found between the ECP434(G>C) and ECP562(G>C) genotypes and smoking habits, lung function and expression of allergic symptoms. Non-allergic asthma was associated with an increased prevalence of the ECP434GG genotype. The ECP c.-38(A>C) genotypes were independently associated to the subject being atopic.Our results show associations of symptoms of allergy and asthma to ECP-genotypes, but also to smoking habits. ECP may be involved in impairment of lung functions in disease. Gender, ethnicity and smoking habits are major confounders in the evaluations of genetic associations to allergy and asthma.The Eosinophil Cationic Protein (ECP), also named RNase 3, is a multifunctional protein with both cytotoxic and fibrogenic properties [1-3]. High levels of ECP were found in blood, bronchoalveolar lavage, saliva and sputum of subjects with allergic asthma indicating the presence of activated eosinophils in the disease process [1,4]. Recently several common polymorphisms were described in the ECP gene [5]. One of these polymorphisms ECP434(G>C) affects the protein coding part of ECP and gives rise to a change in the amino acid arginine at position 97 to threonine [2]. This substitution dramatically alters the function of ECP from a cytotoxic to a non-cytotoxic molecule. Another polymorphism was found in the 3'UTR region ECP562(G>C) and shown to be related to the cellular content of ECP [6]. A third polymorphism was seen in the intron of the ECP gene, ECP c.-38(A>C), and shown by others to be related to serum level
MicroSim: Modeling the Swedish Population  [PDF]
Lisa Brouwers,Martin Camitz,Baki Cakici,Kalle M?kil?,Paul Saretok
Computer Science , 2009,
Abstract: This article presents a unique, large-scale and spatially explicit microsimulation model that uses official anonymized register data collected from all individuals living in Sweden. Individuals are connected to households and workplaces and represent crucial links in the Swedish social contact network. This enables significant policy experiments in the domain of epidemic outbreaks. Development of the model started in 2004 at the Swedish Institute for Infectious Disease Control (SMI) in Solna, Sweden with the goal of creating a tool for testing the effects of intervention policies. These interventions include mass vaccination, targeted vaccination, isolation and social distancing. The model was initially designed for simulating smallpox outbreaks. In 2006, it was modified to support simulations of pandemic influenza. All nine millions members of the Swedish population are represented in the model. This article is a technical description of the simulation model; the input data, the simulation engine and the basic object types.
Swedish in Finland: Pushed Back in the Cyberspace?
László Vincze,Tom Moring
Journal on Ethnopolitics and Minority Issues in Europe , 2012,
Abstract: This article provides an insight into the dynamics of language use among Swedish-speaking Finns regarding two specific aspects of internet use: browsing and blogging. The data was collected from persons with Swedish as their registered mother tongue in 2009. The results indicate a preference for using either Finnish or English when browsing and a preference for Swedish when blogging. Examining the background of these results, we found that people's linguistic environment played an important role in shaping their language competence and language identity, which, in turn, guided their language choice when using the internet. While browsing in Swedish and Finnish was directly affected by language competence, language identity and the composition of linguistic environment, blogging in Swedish and Finnish was only directly affected by language identity.
Swedish snus and the GothiaTek? standard
Lars E Rutqvist, Margareta Curvall, Thord Hassler, Tommy Ringberger, Inger Wahlberg
Harm Reduction Journal , 2011, DOI: 10.1186/1477-7517-8-11
Abstract: The initial impetus for the mentioned changes of the production was quality problems related to microbial activity and formation of ammonia and nitrite in the finished products. Other contributing factors were that snus came under the jurisdiction of the Swedish Food Act in 1971, and concerns that emerged in the 1960s and 1970s about health effects of tobacco, and the significance of agrochemical residues and other potential toxicants in food stuffs.This paper summarizes the historical development of the manufacture of Swedish snus, describes the chemical composition of modern snus, and gives the background and rationale for the GothiaTek? standard, including the selection of constituents for which the standard sets limits. The paper also discusses the potential future of this voluntary standard in relation to current discussions about tobacco harm reduction and regulatory science in tobacco control.The term smokeless tobacco (ST) includes a broad range of products that vary considerably with regard to composition and content of potential toxicants [1,2]. Consequently, there is also a large variability with regard to health effects (this concept is sometimes referred to as "continuum of risk"). The Royal College of Physicians in London stated that "smokeless tobacco is 10-1,000 less hazardous to health than smoking, depending on the product" [3]. In line with this statement, the WHO Tobacco Regulatory Committee (TobReg) recently concluded that "Among the smokeless tobacco products on the market, products with low levels of nitrosamines, such as Swedish snus, are considerably less hazardous than cigarettes..." [2].The health effect profile of Swedish snus and the ability of snus to replace cigarettes among smokers has been evidenced by numerous epidemiological studies [4-6]. Cultural factors have probably contributed to the observed usage patterns. However, the most important determinants of health effects among individual users are the chemical properties of the pro
Adapting research to the 21st century – the Swedish Biobank Register  [cached]
L. Norlin,M. Fransson,S. Eaker,G. Elinder
Norsk Epidemiologi , 2012,
Abstract: In Sweden, there are currently nearly 600 biobanks. The Swedish Biobank Register (SBR) is an on-going national investment by the county councils working to capture information in one database about all biobank samples collected from patients attending the Swedish medical health care. The aim of the SBR is to gather enough information about biobank samples to be able to physically trace the samples. The BioBanking and Molecular Resource Infrastructure of Sweden (BBMRI.se) has been given the task of extending the SBR Information System (IS) with functionality useful for research in connection to health care, quality registers and large patient cohorts. The research extension is called BBMRI catalogue over sample collections for research. To achieve this, the SBR-IS will be extended with attributes useful for both epidemiological and clinical research enabling authorized researchers to search for samples stored at non-clinical biobanks nationwide. The Swedish Biobank Register, together with the BBMRI research catalogue, will be a unique resource for research. SBR-IS will contain information about biobank samples collected by both clinical and population-based biobanks specifically established for research purposes but BBMRI.se researchers will only be granted access to data related to population-based biobanks. As BBMRI.se is the Swedish hub of the pan-European biobank project BBMRI, whose goal is to promote excellence and efficacy in European life science research, the BBMRI research catalogue will also be made compatible with the European register by applying its minimum data set describing biobanks and their objects. In this paper we describe the implementation. Our belief is that it will pave the way for connecting biobanks on an international level as well as stimulate collaborations and optimize usage of biobank samples. In the long run, patients and sample donors will benefit as new results with high statistical power emerge from large scale studies.
AGRICOH: A Consortium of Agricultural Cohorts  [PDF]
Maria E. Leon,Laura E. Beane Freeman,Jeroen Douwes,Jane A. Hoppin,Hans Kromhout,Pierre Lebailly,Karl-Christian Nordby,Marc Schenker,Joachim Schüz,Stephen C. Waring,Michael C.R. Alavanja,Isabella Annesi-Maesano,Isabelle Baldi,Mohamed Aqiel Dalvie,Giles Ferro,Béatrice Fervers,Hilde Langseth,Leslie London,Charles F. Lynch,John McLaughlin,James A. Merchant,Punam Pahwa,Torben Sigsgaard,Leslie Thomas Stayner,Catharina Wesseling,Keun-Young Yoo,Shelia H. Zahm,Kurt Straif,Aaron Blair
International Journal of Environmental Research and Public Health , 2011, DOI: 10.3390/ijerph8051341
Abstract: AGRICOH is a recently formed consortium of agricultural cohort studies involving 22 cohorts from nine countries in five continents: South Africa (1), Canada (3), Costa Rica (2), USA (6), Republic of Korea (1), New Zealand (2), Denmark (1), France (3) and Norway (3). The aim of AGRICOH, initiated by the US National Cancer Institute (NCI) and coordinated by the International Agency for Research on Cancer (IARC), is to promote and sustain collaboration and pooling of data to investigate the association between a wide range of agricultural exposures and a wide range of health outcomes, with a particular focus on associations that cannot easily be addressed in individual studies because of rare exposures (e.g., use of infrequently applied chemicals) or relatively rare outcomes (e.g., certain types of cancer, neurologic and auto-immune diseases). To facilitate future projects the need for data harmonization of selected variables is required and is underway. Altogether, AGRICOH provides excellent opportunities for studying cancer, respiratory, neurologic, and auto-immune diseases as well as reproductive and allergic disorders, injuries and overall mortality in association with a wide array of exposures, prominent among these the application of pesticides.
Obstetric Thromboprophylaxis: The Swedish Guidelines  [PDF]
Pelle G. Lindqvist,Margareta Hellgren
Advances in Hematology , 2011, DOI: 10.1155/2011/157483
Abstract: Obstetric thromboprophylaxis is difficult. Since 10 years Swedish obstetricians have used a combined risk estimation model and recommendations concerning to whom, at what dose, when, and for how long thromboprophylaxis is to be administrated based on a weighted risk score. In this paper we describe the background and validation of the Swedish guidelines for obstetric thromboprophylaxis in women with moderate-high risk of VTE, that is, at similar or higher risk as the antepartum risk among women with history of thrombosis. The risk score is based on major risk factors (i.e., 5-fold increased risk of thromboembolism). We present data on the efficacy of the model, the cost-effectiveness, and the lifestyle advice that is given. We believe that the Swedish guidelines for obstetric thromboprophylaxis aid clinicians in providing women at increased risk of VTE with effective and appropriate thromboprophylaxis, thus avoiding both over- and under-treatment. 1. Introduction The incidence of obstetric venous thromboembolism (VTE) in the Nordic countries is estimated at 10 to 13 cases per 10000 pregnancies, half of them diagnosed during the first six weeks after birth [1, 2]. VTE is one of the most common causes of maternal death [3, 4] and leads to morbidity in the form of postthrombotic syndrome in up to 50–60% [5, 6]. Several factors are known to increase the risk of obstetric VTE, such as personal or family history of VTE, thrombophilia, older age, high body mass index (BMI), immobilization, surgery, smoking, nulliparity, and cancer [1, 2]. Thromboprophylaxis during pregnancy usually consists of daily subcutaneous injections of low molecular weight heparin (LMWH), in combination with compression stockings [7–10]. There are several recommendations concerning how to identify women at high risk of VTE during pregnancy and the puerperium. Some of them divide women into low-medium and high-risk groups [7, 8] and others are based on weighted risk scores [9, 10]. Risk assessment and management of obstetric thromboprophylaxis differ in different countries. The aim of this paper is to describe the background and validation of the Swedish guidelines for obstetric thromboprophylaxis in women with moderate-high risk of VTE. A weighted risk score for estimation of obstetric VTE risk has been used in Sweden for around 10 years. Recommendations concerning to whom, at what dose, when, and for how long thromboprophylaxis is to be administered are based on this risk score. A small number of special cases (women with antithrombin deficiency, antiphospholipid syndrome (APS) with
Association of Autoimmune Addison's Disease with Alleles of STAT4 and GATA3 in European Cohorts  [PDF]
Anna L. Mitchell, Katie D. R. Macarthur, Earn H. Gan, Lucy E. Baggott, Anette S. B. Wolff, Beate Skinningsrud, Hazel Platt, Andrea Short, Anna Lobell, Olle K?mpe, Sophie Bensing, Corrado Betterle, Anna Kasperlik-Zaluska, Magdalena Zurawek, Marta Fichna, Ingrid Kockum, Gabriel Nordling Eriksson, Olov Ekwall, Jeanette Wahlberg, Per Dahlqvist, Anna-Lena Hulting, Marissa Penna-Martinez, Gesine Meyer, Heinrich Kahles, Klaus Badenhoop, Stephanie Hahner, Marcus Quinkler, Alberto Falorni, Amanda Phipps-Green, Tony R. Merriman, William Ollier, Heather J. Cordell, Dag Undlien, Barbara Czarnocka, Eystein Husebye, Simon H. S. Pearce
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088991
Abstract: Background Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for. Aim To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts. Methods A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity. Results We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-κB1 and IL23A genes in the UK and Italian cohorts respectively. Conclusions Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.
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