Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease

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

Constraining resonant photon-axion conversions in the Early Universe

The presence of a primordial magnetic field would have induced resonant conversions between photons and axion-like particles (ALPs) during the thermal history of the Universe. These conversions would have distorted the blackbody spectrum of the cosmic microwave background (CMB). In this context, we derive bounds on the photon-ALP resonant conversions using the high precision CMB spectral data collected by the FIRAS instrument on board of the Cosmic Background Explorer. We obtain upper limits on the product of the photon-ALP coupling constant g times the magnetic field strength B down to g B > 10^{-13} GeV^{-1} nG for ALP masses below the eV scale.Comment: Revised version (19 pages, 3 eps figures). Matches the one published on JCAP. Discussion enlarged in the conclusion

Regulation of tomato fruit growth by epidermal cell wall enzymes

Water relations of tomato fruit and the epidermal and pericarp activities of the putative cell wall loosening and tightening enzymes Xyloglucan endotransglycosylase (XET) and peroxidase were investigated, to determine whether tomato fruit growth is principally regulated in the epidermis or pericarp. Analysis of the fruit water relations and observation of the pattern of expansion of tomato fruit slices in vitro, has shown that the pericarp exerts tissue pressure on the epidermis in tomato fruit, suggesting that the rate of growth of tomato fruit is determined by the physical properties of the epidermal cell walls. The epidermal activities of XET and peroxidase were assayed throughout fruit development. Temporal changes in these enzyme activities were found to correspond well with putative cell wall loosening and stiffening during fruit development. XET activity was found to be proportional to the relative expansion rate of the fruit until growth ceased, and a peroxidase activity weakly bound to the epidermal cell wall appeared shortly before cessation of fruit expansion. No equivalent peroxidase activity was detected in pericarp tissue of any age. It is therefore plausible that the expansion of tomato fruit is regulated by the combined action of these enzyme activities in the fruit epidermis