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 &lt;= 50y, men &gt; 50y, women &lt;= 50y, women &gt; 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&lt; 5%) age-specific effects, of which 11 had larger effects in younger (&lt; 50y) than in older adults (&gt;= 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.</p

Wyoming craton mantle lithosphere: reconstructions based on xenocrysts from Sloan and Kelsey Lake kimberlites

Book synopsis: The structure of the lithospheric mantle of the Wyoming craton beneath two Paleozoic kimberlite pipes, Sloan and Kelsey Lake 1 in Colorado, was reconstructed using single-grain thermobarometry for a large data set (>2,600 EPMA analyses of xenocrysts and mineral intergrowths). Pyrope compositions from both pipes relate to the lherzolitic field (up to 14 wt% Cr2O3) with a few deviations in CaO to harzburgitic field for KL-1 garnets. Clinopyroxene variations (Cr-diopsides and omphacites) from the Sloan pipe show similarities with those from Daldyn kimberlites, Yakutia, and from kimberlites in the central part of the Slave craton, while KL-1 Cpx resemble those from the Alakit kimberlites in Yakutia that sample metasomatized peridotites. LAM ICP analyses recalculated to parental melts for clinopyroxenes from Sloan resemble contaminated protokimberlite melts, while clinopyroxenes from KL-1 show metasomatism by subduction fluids. Melts calculated from garnets from both pipes show peaks for Ba, Sr and U, and HFSE troughs, typical of subduction-related melts. Parental melts calculated for ilmenites from Sloan suggest derivation from highly differentiated melts, or melting of Ilm-bearing metasomatites, while those from Kelsey Lake do not display extreme HFSE enrichment. Three P-Fe# (where Fe# = Fe/(Fe + Mg) in atomic units) trends within the mantle lithosphere beneath Sloan have been obtained using monomineral thermobarometry. At the base, the trends reveal melt metasomatized (possibly sheared) peridotites (Fe# = 13–15 %), refertilized peridotites (Fe# = 10–11 %) and primary mantle peridotites (Fe# = 7–9 %). Anomalous heating was found at depths equivalent to 4.0 and 3.0–2.0 GPa. The mantle section beneath KL-1 is widely metasomatized with several stages of refertilization with dispersed Ilm–Cpx trends. The step-like subadibatic heating in the mantle column beneath the Sloan pipe is strong in the base and the middle part and weaker within 2–3 GPa. Heating beneath the KL-1 pipe is more evident in the base and middle part from 7.0 to 3.0 GPa