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

Production of copolymers with a predefined intermolecular chemical composition distribution by emulsion polymerisation in a continuously operated reactor

The influence of residence time distribution on the intermolecular chemical composition distribution (CCD) for the emulsion copolymerisation of styrene and methyl acrylate has been investigated. A special tubular reactor, the pulsed packed column (PPC), has been used. The PPC combines intensive radial mixing with limited axial mixing, thus providing good heat transfer to the reactor wall and proper emulsification for low net flow rates. A simple backmixing model was developed for feed stream mixing in the PPC. A combination of this backmixing model with a simple mechanistic model for emulsion copolymerisation was used to calculate the CCD of the PPC product. Experimental and calculated results are in good agreement. Production of copolymer having a bimodal CCD in the PPC is compared to the performance of a semi-batch process. The two processes are similar in terms of conversion; however, the CCD of the PPC product shows a characteristic difference. In the PPC some copolymer with an intermediate chemical composition is formed through backmixing of side feed streams. This work demonstrates that the PPC is a promising alternative for semi-batch processes, although some product characteristics will be slightly different

Production of copolymer latexes in continuously operated reactors

The outcome of an emulsion copolymerization in terms of the intermolecular chemical composition distribution (CCD) for example strongly depends on the reactor type and the method of operation. It is demonstrated that homogeneous copolymers as well as copolymers with a bimodal CCD can be produced by seeded emulsion copolymerization of styrene and methyl acrylate in a series of CSTRs