Cross-sectional analysis of sleep hours and quality with sex hormones in men

Background: Reduced total hours of sleep and low quality of sleep have been suggested to be associated with low levels of male hormones. Few studies have examined the association between excessive sleep and male reproductive hormones. Objective: To investigate the association of total hours of sleep and quality of sleep with serum levels of total, bioavailable and free testosterone (tT, bT and fT), sex hormone-binding globulin (SHBG) and dehydroepiandrosteron-sulfate (DHEAS). Methods: Serum levels of tT, SHBG and DHEAS were measured with immunoassays in a cross-sectional population-based study of 2095 males. bT and fT were calculated in accordance with Vermeulens method. Information on total hours of sleep and sleep quality was obtained by questionnaire. Linear regression was used to calculate hormones according to total hours of sleep and the results were expressed as β-estimates and 95% confidence intervals (CI). The adjustment in the multivariable models was constructed taking age, BMI, smoking, alcohol intake and physical activity into account. Results: Excessive sleep (>9 h) compared to 7–9 h of sleep was significantly associated with lower tT, bT and fT, but not with SHBG or DHEAS, after multivariable adjustment. These significant associations were also found in our analyses with hormones as continuous variables but no associations were found in our general additive model analyses. Conclusions: In this cross-sectional study in men, excessive sleep associated with lower levels of male reproductive hormones. Longitudinal studies are needed to determine the causal direction of the observed association between excessive sleep and lower male reproductive hormones levels

Urinary metabolomics reveals glycemic and coffee associated signatures of thyroid function in two population-based cohorts

Triiodothyronine (T3) and thyroxine (T4) as the main secretion products of the thyroid affect nearly every human tissue and are involved in a broad range of processes ranging from energy expenditure and lipid metabolism to glucose homeostasis. Metabolomics studies outside the focus of clinical manifest thyroid diseases are rare. The aim of the present investigation was to analyze the cross-sectional and longitudinal associations of urinary metabolites with serum free T4 (FT4) and thyroid-stimulating hormone (TSH).Urine Metabolites of participants of the population-based studies Inter99 (n = 5620) and Health2006/Health2008 (n = 3788) were analyzed by 1H-NMR spectroscopy. Linear or mixed linear models were used to detect associations between urine metabolites and thyroid function.Cross-sectional analyses revealed positive relations of alanine, trigonelline and lactic acid with FT4 and negative relations of dimethylamine, glucose, glycine and lactic acid with log(TSH). In longitudinal analyses, lower levels of alanine, dimethylamine, glycine, lactic acid and N,N-dimethylglycine were linked to a higher decline in FT4 levels over time, whereas higher trigonelline levels were related to a higher FT4 decline. Moreover, the risk of hypothyroidism was higher in subjects with high baseline trigonelline or low lactic acid, alanine or glycine values.The detected associations mainly emphasize the important role of thyroid hormones in glucose homeostasis. In addition, the predictive character of these metabolites might argue for a potential feedback of the metabolic state on thyroid function. Besides known metabolic consequences of TH, the link to the urine excretion of trigonelline, a marker of coffee consumption, represents a novel finding of this study and given the ubiquitous consumption of coffee requires further research

A 17 year experience in perioperative anaphylaxis 1998-2015: harmonising optimal detection of mast cell mediator release.

BACKGROUND: Sheffield NARCOS (National Adverse Reactions Advisory Service) investigates suspected perioperative anaesthetic reactions using serial tryptase, urinary methylhistamine and clinical information. Further recommendations for additional allergy clinic assessment are provided. OBJECTIVE: To establish a robustly measurable protocol for identifying mast cell mediator (MMR) release in this cohort. To compare these thresholds with previous suggested thresholds and algorithms. METHOD: A review of 3,455 NARCOS cases referred with a suspected peri-operative allergic reaction. Tryptase, Urinary methylhistamine (UMH) and clinical details were analysed. 1746 cases were graded using the Ring and Messmer scale. Reaction grade, tryptase and UMH changes were compared with statistical and graphical presentations appropriate to non-normally distributed measurements using Analyse-IT software. RESULTS: Sensitive strategies such as 3μg/l or 20% are measurable, translatable and would substantially increase detection of potentially relevant changes in tryptases. Adequate quality assurance for low level measurement is needed. An incremental threshold of 20% would identify potential MMR in an additional 14% of cases with peak tryptase (Tp) between 5 and 14 μg/L and a further 15% with Tp below 5 μg/L. Further work is required to establish the diagnostic performance characteristics of this more sensitive approach. UMH also identified up to 120 further cases of potential MMR in absence of tryptase increments. CONCLUSION AND CLINICAL RELEVANCE: Future studies should establish and compare the predictive performance characteristics of each strategy against clinical phenotypes. A single agreed definition of positive serial tryptases is needed to enable robust evaluation of diagnostic strategies. This could serve as a harmonised standard for comparative studies of case series from different centres. This article is protected by copyright. All rights reserved

A novel rare CUBN variant and three additional genes identified in Europeans with and without diabetes : results from an exome-wide association study of albuminuria

Aims/hypothesisIdentifying rare coding variants associated with albuminuria may open new avenues for preventing chronic kidney disease and end-stage renal disease, which are highly prevalent in individuals with diabetes. Efforts to identify genetic susceptibility variants for albuminuria have so far been limited, with the majority of studies focusing on common variants.MethodsWe performed an exome-wide association study to identify coding variants in a two-stage (discovery and replication) approach. Data from 33,985 individuals of European ancestry (15,872 with and 18,113 without diabetes) and 2605 Greenlanders were included.ResultsWe identified a rare (minor allele frequency [MAF]: 0.8%) missense (A1690V) variant in CUBN (rs141640975, =0.27, p=1.3x10(-11)) associated with albuminuria as a continuous measure in the combined European meta-analysis. The presence of each rare allele of the variant was associated with a 6.4% increase in albuminuria. The rare CUBN variant had an effect that was three times stronger in individuals with type 2 diabetes compared with those without (p(interaction)=7.0x10(-4), with diabetes=0.69, without diabetes=0.20) in the discovery meta-analysis. Gene-aggregate tests based on rare and common variants identified three additional genes associated with albuminuria (HES1, CDC73 and GRM5) after multiple testing correction (p(Bonferroni)Peer reviewe

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium

AbstractObservational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P &lt; 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P &lt; 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.</jats:p

Meta-analysis of exome array data identifies six novel genetic loci for lung function

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease