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  • 1
    In: British Journal of Nutrition, 2011, Vol.106(9), pp.1433-1440
    Description: Higher vitamin D concentrations have been proposed as a protective ‘seasonal stimulus’ against influenza, and there are suggestions for associations with other aspects of respiratory health. The aim of the present study was to investigate the relationship of current vitamin D status (measured by 25-hydroxyvitamin D, 25(OH)D) with respiratory infections and lung function. We used cross-sectional data from 6789 participants in the nationwide 1958 British birth cohort who had measurements of 25(OH)D, lung function (forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC)) and respiratory infections available from the age of 45 years. In this population, the prevalence of respiratory infections had a strong seasonal pattern in the opposite direction to the pattern for 25(OH)D concentrations. Each 10 nmol/l increase in 25(OH)D was associated with a 7 % lower risk of infection (95 % CI 3, 11 %) after adjustment for adiposity, lifestyle and socio-economic factors. For FEV 1 and FVC, each 10 nmol/l increase in 25(OH)D was associated with 8 (95 % CI 3, 13) ml and 13 (95 % CI 7, 20) ml higher volume, respectively, after controlling for covariates. Associations of 25(OH)D with FEV 1 and FVC were only slightly attenuated after further adjustment for infection and other respiratory illness. In conclusion, vitamin D status had a linear relationship with respiratory infections and lung function. Randomised controlled trials are warranted to investigate the role of vitamin D supplementation on respiratory health and to establish the underlying mechanisms.
    Keywords: Dietary Surveys And Nutritional Epidemiology; 25-hydroxyvitamin D; Respiratory Infections; Lung Function
    ISSN: 0007-1145
    E-ISSN: 1475-2662
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  • 2
    Language: English
    In: PLoS ONE, 2012, Vol.7(5), p.e37465
    Description: Mendelian randomization (MR) studies use genetic variants mimicking the influence of a modifiable exposure to assess and quantify a causal association with an outcome, with an aim to avoid problems with confounding and reverse causality affecting other types of observational studies. ; We evaluated genetic markers that index differences in 25-hydroxyvitamin D (25(OH)D) as instruments for MR studies on vitamin D. ; We used data from up-to 6,877 participants in the 1958 British birth cohort with information on genetic markers and 25(OH)D. As potential instruments, we selected 20 single nucleotide polymorphisms (SNP) which are located in the vitamin D metabolism pathway or affect skin pigmentation/tanning, including 4 SNPs from genome-wide association (GWA) meta-analyses on 25(OH)D. We analyzed SNP associations with 25(OH)D and evaluated the use of allele scores dividing genes to those affecting 25(OH)D synthesis () and metabolism (). In addition to the GWA SNPs, only two SNPs (, ) showed evidence for association with 25(OH)D, with the association abolished after lifestyle adjustment. Per allele differences varied between −0.02 and −0.08 nmol/L (≤0.02 for all), with a 6.1 nmol/L and a 10.2 nmol/L difference in 25(OH)D between individuals with highest compared lowest number of risk alleles in synthesis and metabolism allele scores, respectively. Individual SNPs but not allele scores showed associations with lifestyle factors. An exception was geographical region which was associated with synthesis score. Illustrative power calculations (80% power, 5% alpha) suggest that approximately 80,000 participants are required to establish a causal effect of vitamin D on blood pressure using the synthesis allele score. ; Combining SNPs into allele scores provides a more powerful instrument for MR analysis than a single SNP in isolation. Population stratification and the potential for pleiotropic effects need to be considered in MR studies on vitamin D.
    Keywords: Research Article ; Biology ; Medicine ; Genetics And Genomics ; Public Health And Epidemiology ; Computational Biology
    E-ISSN: 1932-6203
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  • 3
    Language: English
    In: Occupational and Environmental Medicine, 20 December 2011, Vol.68(12), p.902
    Description: To assess the association between working patterns and vitamin D status in men and women and to determine the potential influence of related lifestyle and socioeconomic factors.
    Keywords: Vitamin D ; Occupational Status ; Health Behaviour ; Epidemiology ; Public Health ; Nutrition ; Preventive Medicine ; Shift Work
    ISSN: 1351-0711
    ISSN: 13510711
    E-ISSN: 1470-7926
    E-ISSN: 14707926
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  • 4
    Language: English
    In: Clinical Nutrition, October 2013, Vol.32(5), pp.758-764
    Description: The relationship between vitamin D and common mental disorders (CMDs) remains unclear. We aimed to determine if behaviours affecting vitamin D concentrations differ between individuals with or without CMDs and evaluate, cross-sectionally and prospectively, the extent to which the association between 25(OH)D and CMDs are explained by these behaviours. Data are from the 1958 British birth cohort (  = 7401). Behaviours were ascertained by questionnaire at age 45 years. CMDs (depression, anxiety, panic, phobia) were assessed using the Clinical Interview Schedule-Revised at 45 years and depression using Mental Health Inventory-5 at 50 years. Participants with CMDs at 45 years differed from others on some but not all vitamin D related behaviours. There were inverse, cross-sectional associations at 45 years of 25(OH)D with depression and panic, which persisted after adjustment for vitamin D related behaviours (OR = 0.57, 95% CI: 0.40,0.81 and OR = 0.33, 95% CI: 0.40,0.81, respectively). Association between 25(OH)D and subsequent (50 years) risk of depression was non-linear (  = 0.01), with lower risk for participants with 25(OH)D between 50 and 85 nmol/l compared with those with lower or higher concentrations. This study provides support for an association of low 25(OH)D concentrations with current and subsequent risk of depression in mid-adulthood.
    Keywords: 25-Hydroxyvitamin D ; Vitamin D ; Mental Health ; Common Mental Disorders ; Depressive Symptoms ; 1958 British Birth Cohort ; Medicine ; Diet & Clinical Nutrition
    ISSN: 0261-5614
    E-ISSN: 1532-1983
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  • 5
    Language: English
    In: Chronobiology International, 01 July 2013, Vol.30(6), pp.786-795
    Description: Seasonal variations in health outcomes are commonly used to hypothesize a link with nutritional vitamin D (25-hydroxyvitamin D, 25(OH)D) status. The majority of vitamin D intake is from skin exposure to sunlight and varies seasonally in countries at a distance away from the Equator. However,...
    Keywords: 25(Oh)D ; Bayesian Analysis ; Harmonic Function ; Hemostatic ; Inflammation ; Mediation Analysis ; Product of Coefficients Test ; Seasonal Variations ; Medicine ; Biology
    ISSN: 0742-0528
    E-ISSN: 1525-6073
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  • 6
    In: Journal of Clinical Laboratory Analysis, May 2017, Vol.31(3), pp.n/a-n/a
    Description: Byline: Diane J. Berry, John Dutton, William D. Fraser, Marjo-Riitta Jarvelin, Elina Hypponen Keywords: 25(OH)D; assay; limits of agreement; population study; reliability; replication; vitamin D 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)D.sub.3 and 25(OH)D.sub.2 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.
    Keywords: 25 Oh D ; Assay ; Limits Of Agreement ; Population Study ; Reliability ; Replication ; Vitamin D
    ISSN: 0887-8013
    E-ISSN: 1098-2825
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  • 7
    Language: English
    In: Diabetes, February 2008, Vol.57(2), pp.298-305
    Description: Hypovitaminosis D and reduced IGF-1 are associated, individually, with metabolic syndrome. Physiological interactions between vitamin D and IGF-1 are reported; this is the first study to investigate their combined associations with metabolic syndrome prevalence. Data on 25-hydroxyvitamin D (25(OH)D), IGF-1, and metabolic syndrome abnormalities (abdominal obesity; raised A1C, blood pressure, and triglycerides; and low HDL cholesterol) were collected from 6,810 British white subjects in the 1958 cohort, surveyed during 2002-2004 (age 45 years). IGF-1 concentrations increased with 25(OH)D up to approximately 75-85 nmol/l but not thereafter. Both 25(OH)D and IGF-1 were inversely associated with metabolic syndrome. There was an interaction between 25(OH)D and IGF-1 (P = 0.025) on metabolic syndrome prevalence: IGF-1 was not significantly associated with metabolic syndrome among those with the lowest levels of 25(OH)D (P 〉 0.09), whereas higher 25(OH)D was associated with metabolic syndrome at all IGF-1 concentrations (P 〈/= 0.006). Metabolic syndrome prevalence was lowest for participants with the highest concentrations of both 25(OH)D and IGF-1 (odds ratio for highest vs. lowest third of both 0.26 [95% CI 0.17-0.40], P 〈 0.0001; adjusted for sex, month, hour, inactivity, alcohol consumption, smoking, and social class). 25(OH)D was associated with the prevalence of high A1C, blood pressure, and triglycerides after adjustment for IGF-1, obesity, and social and lifestyle variations (P 〈/= 0.004 for all comparisons). Serum 25(OH)D is inversely associated with metabolic syndrome, whereas the inverse association with IGF-1 was found only among those without hypovitaminosis D. These results suggest that metabolic syndrome prevalence is the lowest when both 25(OH)D and IGF-1 are high.
    Keywords: Insulin-Like Growth Factor I -- Metabolism ; Metabolic Syndrome -- Blood ; Vitamin D -- Analogs & Derivatives
    ISSN: 00121797
    E-ISSN: 1939-327X
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  • 8
    Language: English
    In: JAMA, 15 March 2016, Vol.315(11), pp.1129-40
    Description: Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain. To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included. Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level. Offspring birth weight from 18 studies. Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P = 7 × 10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P = 1×10(-5)), respectively. A 1-SD ( ≈ 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD ( ≈ 7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD ( ≈ 10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions. In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.
    Keywords: Body Mass Index ; Birth Weight -- Genetics ; Blood Glucose -- Genetics ; Fasting -- Blood ; Obesity -- Genetics
    ISSN: 00987484
    E-ISSN: 1538-3598
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  • 9
    Language: English
    In: BMC Genetics, March 19, 2014, Vol.15(1)
    Description: Background Low vitamin D status has been shown to be a risk factor for several metabolic traits such as obesity, diabetes and cardiovascular disease. The biological actions of 1, 25-dihydroxyvitamin D, are mediated through the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptor, gamma (RXRG). Hence, we examined the potential interactions between the tagging polymorphisms in the VDR (22 tag SNPs) and RXRG (23 tag SNPs) genes on metabolic outcomes such as body mass index, waist circumference, waist-hip ratio (WHR), high- and low-density lipoprotein (LDL) cholesterols, serum triglycerides, systolic and diastolic blood pressures and glycated haemoglobin in the 1958 British Birth Cohort (1958BC, up to n = 5,231). We used Multifactor- dimensionality reduction (MDR) program as a non-parametric test to examine for potential interactions between the VDR and RXRG gene polymorphisms in the 1958BC. We used the data from Northern Finland Birth Cohort 1966 (NFBC66, up to n = 5,316) and Twins UK (up to n = 3,943) to replicate our initial findings from 1958BC. Results After Bonferroni correction, the joint-likelihood ratio test suggested interactions on serum triglycerides (4 SNP - SNP pairs), LDL cholesterol (2 SNP - SNP pairs) and WHR (1 SNP - SNP pair) in the 1958BC. MDR permutation model testing analysis showed one two-way and one three-way interaction to be statistically significant on serum triglycerides in the 1958BC. In meta-analysis of results from two replication cohorts (NFBC66 and Twins UK, total n = 8,183), none of the interactions remained after correction for multiple testing (P.sub.interaction 〉0.17). Conclusions Our results did not provide strong evidence for interactions between allelic variations in VDR and RXRG genes on metabolic outcomes; however, further replication studies on large samples are needed to confirm our findings. Keywords: VDR, RXRG, SNPs, SNP-SNP interaction, 1958BC
    Keywords: Single Nucleotide Polymorphisms -- Analysis ; Glycosylated Hemoglobin -- Analysis ; Cardiovascular Diseases -- Analysis
    ISSN: 1471-2156
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  • 10
    In: European Heart Journal, 2012, Vol. 33(3), pp.393-407
    Description: AIMS: To evaluate the associations of emergent genome-wide-association study-derived coronary heart disease (CHD)-associated single nucleotide polymorphisms (SNPs) with established and emerging risk factors, and the association of genome-wide-association study-derived lipid-associated SNPs with other risk factors and CHD events.METHODS AND RESULTS: Using two case-control studies, three cross-sectional, and seven prospective studies with up to 25 000 individuals and 5794 CHD events we evaluated associations of 34 genome-wide-association study-identified SNPs with CHD risk and 16 CHD-associated risk factors or biomarkers. The Ch9p21 SNPs rs1333049 (OR 1.17; 95% confidence limits 1.11-1.24) and rs10757274 (OR 1.17; 1.09-1.26), MIA3 rs17465637 (OR 1.10; 1.04-1.15), Ch2q36 rs2943634 (OR 1.08; 1.03-1.14), APC rs383830 (OR 1.10; 1.02, 1.18), MTHFD1L rs6922269 (OR 1.10; 1.03, 1.16), CXCL12 rs501120 (OR 1.12; 1.04, 1.20), and SMAD3 rs17228212 (OR 1.11; 1.05, 1.17) were all associated with CHD risk, but not with the CHD biomarkers and risk factors measured. Among the 20 blood lipid-related SNPs, LPL rs17411031 was associated with a lower risk of CHD (OR 0.91; 0.84-0.97), an increase in Apolipoprotein AI and HDL-cholesterol, and reduced triglycerides. SORT1 rs599839 was associated with CHD risk (OR 1.20; 1.15-1.26) as well as total- and LDL-cholesterol, and apolipoprotein B. ANGPTL3 rs12042319 was associated with CHD risk (OR 1.11; 1.03, 1.19), total- and LDL-cholesterol, triglycerides, and interleukin-6.CONCLUSION: Several SNPs predicting CHD events appear to involve pathways not currently indexed by the established or emerging risk factors; others involved changes in blood lipids including triglycerides or HDL-cholesterol as well as LDL-cholesterol. The overlapping association of SNPs with multiple risk factors and biomarkers supports the existence of shared points of regulation for these phenotypes.
    Keywords: Coronary Disease ; Lipids ; Genes ; Risk Factors
    ISSN: 0195-668X
    E-ISSN: 1522-9645
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