The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

A Case Study of Ozone Production in a Rural Area of Central Ontario

An O3 episode observed at Dorset, a rural site in central Ontario, during a stagnant high pressure period of the intensive Eulerian Model Evaluation Field Study (EMEFS), in the summer of 1988, is simulated using a photochemical box model with a two-layer treatment. In the model analysis, natural hydrocarbon chemistry is simulated based on an isoprene-only scenario. Sensitivity tests indicate that local isoprene emissions are an important contributor to local O3 production, relative to anthropogenic hydrocarbons (AHCs), during the event. The model calculated isoprene contribution to the local O3 production, defined as the ratio of the O3 amount formed in the absence of AHCs to that in the presence of AHCs, is characterized by a strong NOx dependence. A minimum value (50%) of the contribution was found at a NOx level of 6 ppbv for the representative hydrocarbon composition during the episode. At this NOx level, O3 production was strongly influenced by the presence of AHCs. At significantly higher or lower NOx levels, isoprene is more important than AHCs in the local O3 production

Determination of the Relative Ozone and PAN Deposition Velocities at Night

A series of measurements of PAN and ozone was conducted during summer at three rural sites in Canada: Egbert and Dorset, Ontario, and Kejimkujik, Nova Scotia. For nights when a stable surface inversion layer forms, ozone and PAN at the surface are found to undergo first order decay, assumed to be due only to dry deposition. Analysis of the measurement data leads to determination of the relative dry deposition velocities. For all three sites, we find that Vd(O3)/Vd(PAN) = 0.42±0.19, at night. This ratio is roughly a factor of 5–6 times smaller than previously assumed. This smaller relative deposition velocity ratio can have a significant impact on model estimations of PAN concentrations near the surface. We estimate that for these sites, the PAN deposition velocity is at least 0.5 cm/s, and may be greater during daytime. This can have a significant impact on the tropospheric lifetime of PAN

Definitions of terms relating to phase transitions of the solid state

Definitions of phase transitions that relate specifically to the solid state are presented. Various types of transition have been defined; they include: (i) structural transitions of the solid state, (ii) transitions related to the change in the state of matter, i.e., from a solid phase to either a liq. or gaseous phase, or vice-versa, (iii) transitions related to changes in compn., (i.v.) metallurgical transitions, (v) transitions related to changes in the electronic structures of crystals, (vi) transitions that change thermodn. properties or the disorder of a system, and (vii) liq.-crystal transitions. [on SciFinder (R)

Definitions of terms relating to phase transitions of the solid state

Definitions of phase transitions that relate specifically to the solid state are presented. Various types of transition have been defined; they include: (i) structural transitions of the solid state, (ii) transitions related to the change in the state of matter, i.e., from a solid phase to either a liq. or gaseous phase, or vice-versa, (iii) transitions related to changes in compn., (i.v.) metallurgical transitions, (v) transitions related to changes in the electronic structures of crystals, (vi) transitions that change thermodn. properties or the disorder of a system, and (vii) liq.-crystal transitions. [on SciFinder (R)