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

Survivorship and longevity of Diamesa mendotae Muttkowski (Diptera: Chironomidae) under snow

Diamesa mendotae Muttkowski commonly grow and emerge from groundwater dominated streams in winter. Previous estimates of longevity for adults of D. mendotae collected from the snow surface averaged 18.6 days post-collection, with 76.9% of individuals dying between Day 10 and Day 30 post-collection and 4.4% surviving over 40 days. Maximum longevities for males and females were 48 and 54 days, respectively. In this paper, we report survivorship and longevity of fieldcollected adults of D. mendotae kept at ambient snow temperature conditions. Adults (n=140) were collected in February from snow along groundwater-dominated sections of the Kinnickinnic River (Wisconsin, USA). All individuals were placed in vials, buried in snow, and retrieved in batches of 10 males and 10 females at 4-day intervals for 28 days. Once retrieved, adults were maintained at 6°C in controlled environmental chambers to determine survivorship and longevity. All individuals survived snow burial treatment, indicating they are capable of surviving sub-freezing field conditions for at least 28 days. Estimates of adult maximum longevity were as high as 66 days, higher than previous estimates for this genus. Our results suggest adults of D. mendotae can persist under snow cover, with high survivorship and longevity, potentially increasing their probability of successful reproduction in regions where lethal winter air temperatures occur