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We assessed the causal relation of four glycemic traits and type 2 diabetes liability with 167 metabolites using Mendelian randomization with various sensitivity analyses and a reverse Mendelian randomization analysis. We extracted instruments for fasting glucose, 2-h glucose, fasting insulin, and glycated hemoglobin from the Meta-Analyses of Glucose and Insulin-related traits Consortium (n = 200,622), and those for type 2 diabetes liability from a meta-analysis of multiple cohorts (148,726 cases, 965,732 controls) in Europeans. Outcome data were from summary statistics of 167 metabolites from the UK Biobank (n = 115,078). Fasting glucose and 2-h glucose were not associated with any metabolite. Higher glycated hemoglobin was associated with higher free cholesterol in small low-density lipoprotein. Type 2 diabetes liability and fasting insulin were inversely associated with apolipoprotein A1, total cholines, lipoprotein subfractions in high-density-lipoprotein and intermediate-density lipoproteins, and positively associated with aromatic amino acids. These findings indicate hyperglycemia-independent patterns and highlight the role of insulin in type 2 diabetes development. Further studies should evaluate these glycemic traits in type 2 diabetes diagnosis and clinical management.

Background Mendelian randomization (MR) studies show iron positively associated with type 2 diabetes (T2D) but included potentially biasing hereditary haemochromatosis variants and did not assess reverse causality. Methods We assessed the relation of iron homeostasis with T2D and glycaemic traits bidirectionally, using genome-wide association studies (GWAS) of iron homeostasis biomarkers [ferritin, serum iron, total iron-binding capacity (TIBC), transferrin saturation (TSAT) (n  ≤ 246 139)], T2D (DIAMANTE n  =   933 970 and FinnGen n  =   300 483), and glycaemic traits [fasting glucose (FG), 2-h glucose, glycated haemoglobin (HbA1c) and fasting insulin (FI) (n  ≤   209 605)]. Inverse variance weighting (IVW) was the main analysis, supplemented with sensitivity analyses and assessment of mediation by hepcidin. Results Iron homeostasis biomarkers were largely unrelated to T2D, although serum iron was potentially associated with higher T2D [odds ratio: 1.07 per standard deviation; 95% confidence interval (CI): 0.99 to 1.16; P- value: 0.078) in DIAMANTE only. Higher ferritin, serum iron, TSAT and lower TIBC likely decreased HbA1c, but were not associated with other glycaemic traits. Liability to T2D likely increased TIBC (0.03 per log odds; 95% CI: 0.01 to 0.05; P- value: 0.005), FI likely increased ferritin (0.29 per log pmol/L; 95% CI: 0.12 to 0.47; P- value: 8.72 x 10–4). FG likely increased serum iron (0.06 per mmol/L; 95% CI: 0.001 to 0.12; P- value: 0.046). Hepcidin did not mediate these associations. Conclusion It is unlikely that ferritin, TSAT and TIBC cause T2D although an association for serum iron could not be excluded. Glycaemic traits and liability to T2D may affect iron homeostasis, but mediation by hepcidin is unlikely. Corresponding mechanistic studies are warranted. [ABSTRACT FROM AUTHOR]

Background Rapid growth is related to adverse respiratory outcomes although possibly confounded or limited by growth modelling methods. We investigated the association of infant and pubertal growth with lung function, wheezing and asthma in a non-Western setting. Methods In Hong Kong's 'Children of 1997' Chinese birth cohort (n  = 8327), weight during infancy and weight, height and body mass index (BMI) during puberty were modelled using a super-imposition by translation and rotation model to identify (larger or smaller) size, (earlier or later) tempo and (slower or faster) velocity. Sex-specific associations with forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC (Global Lung function Initiative z-score) and self-reported wheezing and asthma at ∼17.5 years were assessed. Results For each fraction higher than average weight growth velocity during infancy, FVC was higher in boys (0.90 SD, 95% CI 0.35; 1.44) and girls (0.77 SD, 95% CI 0.24; 1.30), FEV1/FVC was lower (–0.74 SD, 95% CI –1.38; –0.10) and wheezing was higher (odds ratio 6.92, 95% CI 1.60; 29.99) in boys and an inverse association with FVC was observed for tempo but not for size. Associations for weight growth velocity in puberty were similar but weaker. Greater size and higher velocity of BMI growth was associated with higher FVC, lower FEV1/FVC and higher asthma and wheezing risk. Conclusion Accelerated infant and pubertal weight growth were associated with disproportionate lung size and airway growth, and higher risk of asthma; optimizing early-life growth patterns could be important. [ABSTRACT FROM AUTHOR]

Objectives: Adiposity, smoking, and lower socioeconomic position (SEP) increase COVID‐19 risk while the association of vitamin D, blood pressure, and glycemic traits in COVID‐19 risk were less clear. Whether angiotensin‐converting enzyme 2 (ACE2), the key receptor for SARS‐CoV‐2, mediates these associations has not been investigated. We conducted a Mendelian randomization study to assess the role of these exposures in COVID‐19 and mediation by ACE2. Methods: We extracted genetic variants strongly related to various exposures (vitamin D, blood pressure, glycemic traits, smoking, adiposity, and educational attainment [SEP proxy]), and ACE2 cis‐variants from genome‐wide association studies (GWAS, n ranged from 28 204 to 3 037 499) and applied them to GWAS summary statistics of ACE2 (n = 28 204) and COVID‐19 (severe, hospitalized, and susceptibility, n ≤ 2 942 817). We used inverse variance weighted as the main analyses, with MR‐Egger and weighted median as sensitivity analyses. Mediation analyses were performed based on product of coefficient method. Results: Higher adiposity, lifetime smoking index, and lower educational attainment were consistently associated with higher risk of COVID‐19 phenotypes while there was no strong evidence for an association of other exposures in COVID‐19 risk. ACE2 partially mediates the detrimental effects of body mass index (ranged from 4.3% to 8.2%), waist‐to‐hip ratio (ranged from 11.2% to 16.8%), and lower educational attainment (ranged from 4.0% to 7.5%) in COVID‐19 phenotypes while ACE2 did not mediate the detrimental effect of smoking. Conclusions: We provided genetic evidence that reducing ACE2 could partly lower COVID‐19 risk amongst people who were overweight/obese or of lower SEP. [ABSTRACT FROM AUTHOR]

Background: Observationally, poorer maternal respiratory health is associated with poorer birth outcomes, possibly confounded by socioeconomic position and other maternal attributes. We used multivariable Mendelian randomization (MR) to obtain unconfounded estimates of effect of maternal lung function on birthweight, independent of maternal height.Methods: Single nucleotide polymorphisms (SNPs) for forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in women were obtained from publicly available summary statistics from the UK Biobank. SNPs for asthma were obtained from the Trans-National Asthma Genetic consortium. SNPs for height in women were obtained from the Genetic Investigation of Anthropometric Traits consortium and the genetic estimates were obtained the UK Biobank. The genetic associations with maternally-driven birthweight were obtained from the Early Growth Genetics consortium. Multivariable MR estimates were obtained using inverse variance weighting with multivariable MR-Egger as sensitivity analysis.Results: Maternal lung capacity, as indicated by FVC, was positively associated with maternally-driven birthweight (0.08 per standard deviation, 95% confidence interval 0.01 to 0.15) independent of maternal height, whereas no clear such associations were shown for maternal airway function, indicated by FEV1 and peak expiratory flow, or for asthma, on maternally-driven birthweight. Similar findings were shown using MR-Egger.Conclusions: These findings suggest that maternal lung function, especially lung capacity independent of maternal height, is directly associated with maternally-driven birthweight, and highlights the importance of maternal respiratory health in fetal growth. [ABSTRACT FROM AUTHOR]

Background: Information on the relationship between sleep duration and obesity among children in urban Guangzhou, China is limited. This study aims to examine the relationship between sleep duration and obesity in children aged 6-18 years.Methods: The sample consisted of 11,830 children aged 6-18 years. The children were randomly selected from 13 schools in three urban districts of Guangzhou. The study was conducted from September to November 2013. The height and weight of the children were measured. Adiposity status was estimated using body mass index and according to the cut point in China criteria. In the structured questionnaire, children reported daily sleep hours (less than 7 h, 7-9 h and more than 9 h), weekly food intake amount (including vegetables, fruit, sugar beverages and meat), physical activity and sedentary time. A caretaker would answer the questionnaire on behalf of a child aged below nine.Results: A total of 8,760 children (49.0 % boys) completed the study. The prevalence of obesity was 8.4 % (9.8 % in boys and 5.7 % in girls). Adjusted for age, diet and physical activity/sedentary behaviour, the odds ratio (OR) for obesity comparing sleeping <7 h (short sleep duration, SSD) with ≥9 h (long sleep duration, LSD) was 0.70 (95 % CI: 0.69-0.72) among boys and 1.73 (95 % CI: 1.71-1.74) among girls. Stratified by age, OR for boys aged 6-12 years comparing SSD with LSD was 0.60 (95 % CI: 0.55-0.66); by contrast, OR was 1.33 (95 % CI: 1.30-1.37) for boys aged 13-18 years.Conclusion: Short sleep duration is associated with increased chances of obesity among girls and 13- to 18-year-old boys, but the chances of obesity are decreased among 6- to 12-year-old boys. Age and gender should be regarded as specific characteristics for the effects of short sleep on obesity. [ABSTRACT FROM AUTHOR]