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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]

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]