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

Sub-hertz fundamental linewidth photonic integrated Brillouin laser

Photonic systems and technologies traditionally relegated to table-top experiments are poised to make the leap from the laboratory to real-world applications through integration. Stimulated Brillouin scattering (SBS) lasers, through their unique linewidth narrowing properties, are an ideal candidate to create highly-coherent waveguide integrated sources. In particular, cascaded-order Brillouin lasers show promise for multi-line emission, low-noise microwave generation and other optical comb applications. Photonic integration of these lasers can dramatically improve their stability to environmental and mechanical disturbances, simplify their packaging, and lower cost. While single-order silicon and cascade-order chalcogenide waveguide SBS lasers have been demonstrated, these lasers produce modest emission linewidths of 10-100 kHz. We report the first demonstration of a sub-Hz (~0.7 Hz) fundamental linewidth photonic-integrated Brillouin cascaded-order laser, representing a significant advancement in the state-of-the-art in integrated waveguide SBS lasers. This laser is comprised of a bus-ring resonator fabricated using an ultra-low loss Si3N4 waveguide platform. To achieve a sub-Hz linewidth, we leverage a high-Q, large mode volume, single polarization mode resonator that produces photon generated acoustic waves without phonon guiding. This approach greatly relaxes phase matching conditions between polarization modes, and optical and acoustic modes. Using a theory for cascaded-order Brillouin laser dynamics, we determine the fundamental emission linewidth of the first Stokes order by measuring the beat-note linewidth between and the relative powers of the first and third Stokes orders. Extension to the visible and near-IR wavebands is possible due to the low optical loss from 405 nm to 2350 nm, paving the way to photonic-integrated sub-Hz lasers for visible-light applications