Publications
976 results found
January SA, Mason WA, Savolainen J, et al., 2016, Longitudinal pathways from cumulative contextual risk at birth to school functioning in adolescence: analysis of mediation effects and gender moderation, Journal of Youth and Adolescence, Vol: 46, Pages: 180-196, ISSN: 1573-6601
Children and adolescents exposed to multiple contextual risks are more likely to have academic difficulties and externalizing behavior problems than those who experience fewer risks. This study used data from the Northern Finland Birth Cohort 1986 (a population-based study; N = 6961; 51 % female) to investigate (a) the impact of cumulative contextual risk at birth on adolescents' academic performance and misbehavior in school, (b) learning difficulties and/or externalizing behavior problems in childhood as intervening mechanisms in the association of cumulative contextual risk with functioning in adolescence, and (c) potential gender differences in the predictive associations of cumulative contextual risk at birth with functioning in childhood or adolescence. The results of the structural equation modeling analysis suggested that exposure to cumulative contextual risk at birth had negative associations with functioning 16 years later, and academic difficulties and externalizing behavior problems in childhood mediated some of the predictive relations. Gender, however, did not moderate any of the associations. Therefore, the findings of this study have implications for the prevention of learning and conduct problems in youth and future research on the impact of cumulative risk exposure.
Surendran P, Drenos F, Young R, et al., 2016, Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension, Nature Genetics, Vol: 48, Pages: 1151-1161, ISSN: 1546-1718
High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
Ehret GB, Ferreira T, Chasman DI, et al., 2016, The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals, Nature Genetics, Vol: 48, Pages: 1171-1184, ISSN: 1546-1718
To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
Metcalf SA, Jones PB, Nordstrom T, et al., 2016, Serum C-reactive protein in adolescence and risk of schizophrenia in adulthood: A prospective birth cohort study., Brain, Behavior, and Immunity, Vol: 59, Pages: 253-259, ISSN: 0889-1591
OBJECTIVE: Meta-analyses of cross-sectional studies confirm an increase in circulating inflammatory markers during acute psychosis. Longitudinal studies are scarce but are needed to understand whether elevated inflammatory markers are a cause or consequence of illness. We report a longitudinal study of serum C-reactive protein (CRP) in adolescence and subsequent risk of schizophrenia and related psychoses in adulthood in the Northern Finland Birth Cohort 1986. METHOD: Serum high-sensitivity CRP was measured at age 15/16 years in 6362 participants. ICD-10 diagnoses of schizophrenia and related psychoses were obtained from centralised hospital inpatient and outpatient registers up to age 27 years. Logistic regression calculated odds ratios (ORs) for psychotic outcomes associated with baseline CRP levels analysed as both continuous and categorical variables using American Heart Association criteria. Age, sex, body mass index, maternal education, smoking, and alcohol use were included as potential confounders. RESULTS: By age 27years, 88 cases of non-affective psychosis (1.38%), of which 22 were schizophrenia (0.35%), were identified. Adolescent CRP was associated with subsequent schizophrenia. The adjusted OR for schizophrenia by age 27yearsfor each standard deviation (SD) increase in CRP levels at age 15/16yearswas 1.25 (95% CI, 1.07-1.46), which was consistent with a linear, dose-response relationship (P-value for quadratic term 0.23). Using CRP as a categorical variable, those with high (>3mg/L) compared with low (<1mg/L) CRP levels at baseline were more likely to develop schizophrenia; adjusted OR 4.25 (95% CI, 1.30-13.93). There was some indication that higher CRP was associated with earlier onset of schizophrenia (rs=-0.40; P=0.07). CONCLUSIONS: A longitudinal association between adolescent CRP levels and adult schizophrenia diagnosis indicates a potentially important role of inflammation in the pathogenesis of the illness, although the findings, based on a
Berry DJ, Dutton J, Fraser WD, et al., 2016, Harmonization Study Between LC-MS/MS and Diasorin RIA for Measurement of 25-Hydroxyvitamin D Concentrations in a Large Population Survey., Journal of Clinical Laboratory Analysis, Vol: 31, ISSN: 1098-2825
BACKGROUND: Population-based research on vitamin D has increased dramatically in recent years. Such studies are typically reliant on assay procedures to measure reliable and comparable levels of 25-hydroxyvitamin D [25(OH)D] concentrations. METHODS: Concentrations of 25(OH)D3 and 25(OH)D2 were measured using LC-MS/MS in 5,915 participants (aged 31 years) of Northern Finland Birth Cohort 1966. Blood samples were assayed in batches over a course of 18 months. As anomalies were present in the measurements, 200 samples were reassayed using Diasorin RIA. Agreement between measurements was assessed by Passing-Bablok regression and limits of agreement (LoA). To harmonize LC-MS/MS with Diasorin RIA measurements, formulae were derived from the LoA. RESULTS: Concentrations measured by LC-MS/MS were much higher than those measured by Diasorin RIA, with a mean difference of 12.9 ng/ml. Constant variation was evident between batch measurements after log transformation. Statistical formula was applied separately for each batch of LC-MS/MS measurements, enabling us to remove both the constant and proportional bias that was evident prior to the transformation. CONCLUSION: Despite the introduction of schemes/programs to improve accuracy of assays to measure 25(OH)D, significant differences can still happen. In these instances, methods to harmonize measurements based on a relatively small number of replicates can be successfully applied to establish confidence and to enable between-study comparisons.
Lockett GA, Soto-Ramírez N, Ray MA, et al., 2016, Association of season of birth with DNA methylation and allergic disease., Allergy, Vol: 71, Pages: 1314-1324
BACKGROUND: Season of birth influences allergy risk; however, the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy. METHODS: In a subset of 18-year-old participants from the Isle of Wight (IoW) birth cohort (n = 367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome-wide DNA methylation was measured, and season-associated CpGs detected using a training-and-testing-based technique. Validation method examined the 8-year-old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third-generation cohort newborns. RESULTS: Autumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with season of birth in the epigenome-wide association study. In validation, significantly more CpGs had the same directionality than expected by chance, and four were statistically significant. Season-associated methylation was enriched among networks relating to development, the cell cycle and apoptosis. Twenty CpGs were nominally associated with allergic outcomes. Two CpGs were marginally on the causal pathway to allergy. Season-associated methylation was largely absent in newborns, suggesting it arises post-natally. CONCLUSIONS: This study demonstrates that DNA methylation in adulthood is associated with season of birth, supporting the hypothesis that DNA methylation could mechanistically underlie the effect of season of birth on allergy, although other mechanisms are also likely to be involved.
Kiviniemi AM, Perkiömäu N, Auvinen J, et al., 2016, Lifelong Physical Activity and Cardiovascular Autonomic Function in Midlife, Medicine and Science in Sports and Exercise, Vol: 48, Pages: 1506-1513, ISSN: 1530-0315
PURPOSE: Physical activity (PA) associates with cardiovascular autonomic function, but the relationship with lifelong PA is unclear. We hypothesized that lifelong PA would associate with cardiovascular autonomic function in midlife. METHODS: At the age of 46 yr, the subjects of the prospective Northern Finland Birth Cohort 1966 were invited to examinations where vagally mediated heart rate variability (root mean square of the successive differences in RRi [rMSSD]) and cross-spectral baroreflex sensitivity (BRS) were analyzed from 3-min recordings of ECG and blood pressure in seated and standing positions. Three lifelong PA trajectory groups (active, semiactive, and inactive) were formed according to their self-reported frequencies of participation in PA at the ages of 14, 31, and 46 yr. Finally, 1283 men and 1779 women without cardiorespiratory diseases and diabetes had complete data on lifelong PA, covariates, and rMSSD, and 662 men and 807 women for BRS. RESULTS: In both sexes and measurement conditions, the active (P < 0.01) and semiactive groups (P < 0.05) had greater rMSSD than the inactive group, and the highest BRS was observed in the active group (ANOVA P = 0.001-0.032). In men, these differences were not significant when adjusted for 46-yr lifestyle (smoking, alcohol consumption, sleep, and sitting time), body mass index, waist-to-hip ratio, blood pressure, lipid status, and glucose status. In women, lifelong PA remained a significant independent determinant of seated and standing rMSSD and standing BRS. CONCLUSION: Higher lifelong PA was associated with better cardiovascular autonomic function in midlife. In women, this effect was independent, but in men, it seemed to be mediated by the other lifestyle and cardiometabolic factors.
Wurtz P, Cook S, Wang Q, et al., 2016, Comprehensive metabolic profiling of alcohol consumption in 9778 young adults, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 1131-1132, ISSN: 0195-668X
Wurtz P, Wang Q, Soininen P, et al., 2016, Comprehensive metabolic profiling of statin therapy: longitudinal evidence and Mendelian randomization, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 790-790, ISSN: 0195-668X
Perkiomaki N, Auvinen J, Tulppo MP, et al., 2016, Association between Birth Characteristics and Cardiovascular Autonomic Function at Mid-Life, PLOS One, Vol: 11, ISSN: 1932-6203
BackgroundLow birth weight is associated with an increased risk of cardiovascular diseases in adulthood. As abnormal cardiac autonomic function is a common feature in cardiovascular diseases, we tested the hypothesis that low birth weight may also be associated with poorer cardiac autonomic function in middle-aged subjects.MethodsAt the age of 46, the subjects of the Northern Finland Birth Cohort 1966 were invited to examinations including questionnaires about health status and life style and measurement of vagally-mediated heart rate variability (rMSSD) from R-R intervals (RRi) and spontaneous baroreflex sensitivity (BRS) in both seated and standing positions. Maternal parameters had been collected in 1965–1966 since the 16th gestational week and birth variables immediately after delivery. For rMSSD, 1,799 men and 2,279 women without cardiorespiratory diseases and diabetes were included and 902 men and 1,020 women for BRS. The analyses were adjusted for maternal (age, anthropometry, socioeconomics, parity, gestational smoking) and adult variables (life style, anthropometry, blood pressure, glycemic and lipid status) potentially confounding the relationship between birth weight and autonomic function.ResultsIn men, birth weight correlated negatively with seated (r = -0.058, p = 0.014) and standing rMSSD (r = -0.090, p<0.001), as well as with standing BRS (r = -0.092, p = 0.006). These observations were verified using relevant birth weight categories (<2,500 g; 2,500–3,999 g; ≥4,000 g). In women, birth weight was positively correlated with seated BRS (r = 0.081, p = 0.010), but none of the other measures of cardiovascular autonomic function. These correlations remained significant after adjustment for potential confounders (p<0.05 for all).ConclusionsIn men, higher birth weight was independently associated with poorer cardiac autonomic function at mid-life. Same association was not observed in women. Our findings suggest that higher, not lower
Wang Q, Würtz P, Auro K, et al., 2016, Effects of hormonal contraception on systemic metabolism: cross-sectional and longitudinal evidence, International Journal of Epidemiology, Vol: 45, Pages: 1445-1457, ISSN: 1464-3685
BACKGROUND: Hormonal contraception is commonly used worldwide, but its systemic effects across lipoprotein subclasses, fatty acids, circulating metabolites and cytokines remain poorly understood. METHODS: A comprehensive molecular profile (75 metabolic measures and 37 cytokines) was measured for up to 5841 women (age range 24-49 years) from three population-based cohorts. Women using combined oral contraceptive pills (COCPs) or progestin-only contraceptives (POCs) were compared with those who did not use hormonal contraception. Metabolomics profiles were reassessed for 869 women after 6 years to uncover the metabolic effects of starting, stopping and persistently using hormonal contraception. RESULTS: The comprehensive molecular profiling allowed multiple new findings on the metabolic associations with the use of COCPs. They were positively associated with lipoprotein subclasses, including all high-density lipoprotein (HDL) subclasses. The associations with fatty acids and amino acids were strong and variable in direction. COCP use was negatively associated with albumin and positively associated with creatinine and inflammatory markers, including glycoprotein acetyls and several growth factors and interleukins. Our findings also confirmed previous results e.g. for increased circulating triglycerides and HDL cholesterol. Starting COCPs caused similar metabolic changes to those observed cross-sectionally: the changes were maintained in consistent users and normalized in those who stopped using. In contrast, POCs were only weakly associated with metabolic and inflammatory markers. Results were consistent across all cohorts and for different COCP preparations and different types of POC delivery. CONCLUSIONS: Use of COCPs causes widespread metabolic and inflammatory effects. However, persistent use does not appear to accumulate the effects over time and the metabolic perturbations are reversed upon discontinuation. POCs have little effect on systemic metabolism and infla
Würtz P, Cook S, Wang Q, et al., 2016, Metabolic profiling of alcohol consumption in 9778 young adults, International Journal of Epidemiology, Vol: 45, Pages: 1493-1506, ISSN: 1464-3685
BACKGROUND: High alcohol consumption is a major cause of morbidity, yet alcohol is associated with both favourable and adverse effects on cardiometabolic risk markers. We aimed to characterize the associations of usual alcohol consumption with a comprehensive systemic metabolite profile in young adults. METHODS: Cross-sectional associations of alcohol intake with 86 metabolic measures were assessed for 9778 individuals from three population-based cohorts from Finland (age 24-45 years, 52% women). Metabolic changes associated with change in alcohol intake during 6-year follow-up were further examined for 1466 individuals. Alcohol intake was assessed by questionnaires. Circulating lipids, fatty acids and metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. RESULTS: Increased alcohol intake was associated with cardiometabolic risk markers across multiple metabolic pathways, including higher lipid concentrations in HDL subclasses and smaller LDL particle size, increased proportions of monounsaturated fatty acids and decreased proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate (P < 0.001 for 56 metabolic measures). Many metabolic biomarkers displayed U-shaped associations with alcohol consumption. Results were coherent for men and women, consistent across the three cohorts and similar if adjusting for body mass index, smoking and physical activity. The metabolic changes accompanying change in alcohol intake during follow-up resembled the cross-sectional association pattern (R(2 )= 0.83, slope = 0.72 ± 0.04). CONCLUSIONS: Alcohol consumption is associated with a complex metabolic signature, including aberrations in multiple biomarkers for elevated cardiometabolic risk. The metabolic signature tracks with long-term changes in alcohol consumption. These results elucidate the double-edged effects of alcohol on cardiovascula
Schieck M, Schouten JP, Michel S, et al., 2016, Doublesex and mab-3 related transcription factor 1 (DMRT1) is a sex-specific genetic determinant of childhood-onset asthma and is expressed in testis and macrophages., J Allergy Clin Immunol, Vol: 138, Pages: 421-431
BACKGROUND: Asthma is a disease affecting more boys than girls in childhood and more women than men in adulthood. The mechanisms behind these sex-specific differences are not yet understood. OBJECTIVE: We analyzed whether and how genetic factors contribute to sex-specific predisposition to childhood-onset asthma. METHODS: Interactions between sex and polymorphisms on childhood asthma risk were evaluated in the Multicentre Asthma Genetics in Childhood Study (MAGICS)/Phase II International Study of Asthma and Allergies in Childhood (ISAAC II) population on a genome-wide level, and findings were validated in independent populations. Genetic fine mapping of sex-specific asthma association signals was performed, and putatively causal polymorphisms were characterized in vitro by using electrophoretic mobility shift and luciferase activity assays. Gene and protein expression of the identified gene doublesex and mab-3 related transcription factor 1 (DMRT1) were measured in different human tissues by using quantitative real-time PCR and immunohistochemistry. RESULTS: Polymorphisms in the testis-associated gene DMRT1 displayed interactions with sex on asthma status in a population of primarily clinically defined asthmatic children and nonasthmatic control subjects (lowest P = 5.21 × 10(-6)). Replication of this interaction was successful in 2 childhood populations clinically assessed for asthma but showed heterogeneous results in other population-based samples. Polymorphism rs3812523 located in the putative DMRT1 promoter was associated with allele-specific changes in transcription factor binding and promoter activity in vitro. DMRT1 expression was observed not only in the testis but also in lung macrophages. CONCLUSION: DMRT1 might influence sex-specific patterns of childhood asthma, and its expression in testis tissue and lung macrophages suggests a potential involvement in hormone or immune cell regulation.
Mutt SJ, Lehtonen S, Lehenkari P, et al., 2016, Effect of vitamin D on human mesenchymal stem cells adipogenesis and cytokine secretion in hypoxia, 52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Publisher: SPRINGER, Pages: S289-S290, ISSN: 0012-186X
Bousquet J, Farrell J, Crooks G, et al., 2016, Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)., Clinical and Translational Allergy, Vol: 6, ISSN: 2045-7022
Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
Kanoni S, Masca NG, Stirrups KE, et al., 2016, Analysis with the exome array identifies multiple new independent variants in lipid loci., Human Molecular Genetics, Vol: 25, Pages: 4094-4106, ISSN: 1460-2083
It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were >1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF <5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.
Kantomaa MT, Tikanmäki M, Kankaanpää A, et al., 2016, Accelerometer-Measured Physical Activity and Sedentary Time Differ According to Education Level in Young Adults., PLOS One, Vol: 11, ISSN: 1932-6203
This study examined the association of education level with objectively measured physical activity and sedentary time in young adults. Data from the Finnish ESTER study (2009-2011) (n = 538) was used to examine the association between educational attainment and different subcomponents of physical activity and sedentary time measured using hip-worn accelerometers (ActiGraph GT1M) for seven consecutive days. Overall physical activity, moderate-to-vigorous physical activity (MVPA), light-intensity physical activity and sedentary time were calculated separately for weekdays and weekend days. A latent profile analysis was conducted to identify the different profiles of sedentary time and the subcomponents of physical activity. The educational differences in accelerometer-measured physical activity and sedentary time varied according to the subcomponents of physical activity, and between weekdays and weekend days. A high education level was associated with high MVPA during weekdays and weekend days in both sexes, high sedentary time during weekdays in both sexes, and a low amount of light-intensity physical activity during weekdays in males and during weekdays and weekend days in females. The results indicate different challenges related to unhealthy behaviours in young adults with low and high education: low education is associated with a lack of MVPA, whereas high education is associated with a lack of light-intensity physical activity and high sedentary time especially during weekdays.
Gormley P, Anttila V, Winsvold BS, et al., 2016, Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine, Nature Genetics, Vol: 48, Pages: 856-866, ISSN: 1546-1718
Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10−8) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.
Bray R, Cartwright R, Tikkinen K, et al., 2016, Post partum incontinence and its effect on lower urinary tract symptoms: 12-year follow-up of a population-based prospective cohort, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 123, Pages: 50-51, ISSN: 1470-0328
Ketelaar ME, Nawijn MC, Shaw DE, et al., 2016, The challenge of measuring IL-33 in serum using commercial ELISA: lessons from asthma., Clin Exp Allergy, Vol: 46, Pages: 884-887
BACKGROUND: Interleukin-33 (IL-33) has been subject of extensive study in the context of inflammatory disorders, particularly in asthma. Many human biological samples, including serum, have been used to determine the protein levels of IL-33, aiming to investigate its involvement in asthma. Reliable methods are required to study the association of IL-33 with disease, especially considering the complex nature of serum samples. OBJECTIVE: We evaluated four IL-33 ELISA kits, aiming to determine a robust and reproducible approach to quantifying IL-33 in human serum from asthma patients. METHODS: IL-33 levels were investigated in serum of well-defined asthma patients by the Quantikine, DuoSet (both R&D systems), ADI-900-201 (Enzo Life Sciences), and SKR038 (GenWay Biotech Inc San Diego USA) immunoassays, as well as spiking experiments were performed using recombinant IL-33 and its soluble receptor IL-1RL1-a. RESULTS: We show that 1) IL-33 is difficult to detect by ELISA in human serum, due to lack of sensitivity and specificity of currently available assays; 2) human serum interferes with IL-33 quantification, in part through IL-1RL1-a; and 3) using non-serum certified kits may lead to spurious findings. CONCLUSION AND CLINICAL RELEVANCE: If IL-33 is to be studied in the serum of asthma patients and other diseases, a more sensitive and specific assay method is required, which will be vital for further understanding and targeting of the IL-33/IL-1RL1 axis in human disease.
Majeed F, Hansell A, Saxena S, et al., 2016, How would a decision to leave the European Union affect medical research and health in the United Kingdom?, Journal of the Royal Society of Medicine, Vol: 109, Pages: 216-218, ISSN: 1758-1095
Matinolli H-M, Mannisto S, Sipola-Leppanen M, et al., 2016, Body image and eating behavior in young adults born preterm, International Journal of Eating Disorders, Vol: 49, Pages: 572-580, ISSN: 1098-108X
Okbay A, Beauchamp JP, Fontana MA, et al., 2016, Genome-wide association study identifies 74 loci associated with educational attainment, Nature, Vol: 533, Pages: 539-542, ISSN: 0028-0836
Fuertes E, Markevych I, Bowatte G, et al., 2016, Residential greenness is differentially associated with childhood allergic rhinitis and aeroallergen sensitization in seven birth cohorts, ALLERGY, Vol: 71, Pages: 1461-1471, ISSN: 0105-4538
BackgroundThe prevalence of allergic rhinitis is high, but the role of environmental factors remains unclear. We examined cohort‐specific and combined associations of residential greenness with allergic rhinitis and aeroallergen sensitization based on individual data from Swedish (BAMSE), Australian (MACS), Dutch (PIAMA), Canadian (CAPPS and SAGE), and German (GINIplus and LISAplus) birth cohorts (n = 13 016).MethodsAllergic rhinitis (doctor diagnosis/symptoms) and aeroallergen sensitization were assessed in children aged 6–8 years in six cohorts and 10–12 years in five cohorts. Residential greenness was defined as the mean Normalized Difference Vegetation Index (NDVI) in a 500‐m buffer around the home address at the time of health assessment. Cohort‐specific associations per 0.2 unit increase in NDVI were assessed using logistic regression models and combined in a random‐effects meta‐analysis.ResultsGreenness in a 500‐m buffer was positively associated with allergic rhinitis at 6–8 years in BAMSE (odds ratio = 1.42, 95% confidence interval [1.13, 1.79]) and GINI/LISA South (1.69 [1.19, 2.41]) but inversely associated in GINI/LISA North (0.61 [0.36, 1.01]) and PIAMA (0.67 [0.47, 0.95]). Effect estimates in CAPPS and SAGE were also conflicting but not significant (0.63 [0.32, 1.24] and 1.31 [0.81, 2.12], respectively). All meta‐analyses were nonsignificant. Results were similar for aeroallergen sensitization at 6–8 years and both outcomes at 10–12 years. Stratification by NO2 concentrations, population density, an urban vs rural marker, and moving did not reveal consistent trends within subgroups.ConclusionAlthough residential greenness appears to be associated with childhood allergic rhinitis and aeroallergen sensitization, the effect direction varies by location.
Ierodiakonou D, Portelli MA, Postma DS, et al., 2016, Urokinase plasminogen activator receptor polymorphisms and airway remodelling in asthma, EUROPEAN RESPIRATORY JOURNAL, Vol: 47, Pages: 1568-1571, ISSN: 0903-1936
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Bousquet J, Schünemann HJ, Hellings PW, et al., 2016, MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis, Journal of Allergy and Clinical Immunology, Vol: 138, Pages: 367-374.e2, ISSN: 1097-6825
The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials.
Lehne B, Drong AW, Loh M, et al., 2016, Erratum to: A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies., Genome Biology, Vol: 17, ISSN: 1474-760X
Okbay A, Baselmans BML, De Neve J-E, et al., 2016, Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses, Nature Genetics, Vol: 48, Pages: 624-633, ISSN: 1061-4036
Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρˆ| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
Larsen SC, Ängquist L, Moldovan M, et al., 2016, Serum 25-Hydroxyvitamin D Status and Longitudinal Changes in Weight and Waist Circumference: Influence of Genetic Predisposition to Adiposity., PLOS One, Vol: 11, ISSN: 1932-6203
Studies of the relationship between serum 25-hydroxyvitamin D (25(OH)D) and changes in measures of adiposity have shown inconsistent results, and interaction with genetic predisposition to obesity has rarely been examined. We examined whether 25(OH)D was associated with subsequent annual changes in body weight (ΔBW) or waist circumference (ΔWC), and whether the associations were modified by genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI (WHRBMI). The study was based on 10,898 individuals from the Danish Inter99, the 1958 British Birth Cohort and the Northern Finland Birth Cohort 1966. We combined 42 adiposity-associated Single Nucleotide Polymorphisms (SNPs) into four scores indicating genetic predisposition to BMI, WC and WHRBMI, or all three traits combined. Linear regression was used to examine the association between serum 25(OH)D and ΔBW or ΔWC, SNP-score × 25(OH)D interactions were examined, and results from the individual cohorts were meta-analyzed. In the meta-analyses, we found no evidence of an association between 25(OH)D and ΔBW (-9.4 gram/y per 10 nmol/L higher 25(OH)D [95% CI: -23.0, +4.3; P = 0.18]) or ΔWC (-0.06 mm/y per 10 nmol/L higher 25(OH)D [95% CI: -0.17, +0.06; P = 0.33]). Furthermore, we found no statistically significant interactions between the four SNP-scores and 25(OH)D in relation to ΔBW or ΔWC. Thus, in view of the narrow CIs, our results suggest that an association between 25(OH)D and changes in measures of adiposity is absent or marginal. Similarly, the study provided evidence that there is either no or very limited dependence on genetic predisposition to adiposity.
Mutt SJ, Lehtonen S, Lehenkari P, et al., 2016, Effect of Vitamin D on Adipogenesis under Hypoxia, Experimental Biology Meeting, Publisher: FEDERATION AMER SOC EXP BIOL, ISSN: 0892-6638
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