Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

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

Evaluation of eco-friendly cellulose and lignocellulose nanofibers from rice straw using Multiple Quality Index

International audienceHuge amounts of rice straw are left every year in different areas of the world; these residues still cause environmental problems due to un-safe practices such as burning. Isolation of nanomaterials such as cellulose nanofibers represents an effective way for utilization of rice straw in advanced products. The current work aimed at evaluating the properties of rice straw cellulose nanofibers isolated from bleached and high-lignin unbleached pulps using a multi-criterion quality index, which allows a benchmarking analysis between different sources, processes and features. Rice straw was subjected to neutral sulfite pulping process to obtain the high-lignin unbleached pulp while the bleached pulp was obtained by bleaching the produced pulp with NaClO2/acetic acid mixture. Using mechanical pretreatment (Valley beater), and ultrafine friction grinder both bleached and unbleached pulps were used to obtain cellulose nanofibers with and without lignin (L-CNF and CNF, respectively). Nanopaper sheets were prepared from both types of nanofibers and characterized using tensile tests, optical microscopy, atomic force microscopy, electron scanning microscopy, water contact angle and surface energy. Cellulose nanofibers generated from rice straw were scored using a multi-criterion quality index depending on characterization using eight tests (nanosized and macro size fraction, turbidity, Young's modulus, porosity, transmittance, tear resistance, and homogeneity)

The role of diffusion weighted magnetic resonance imaging in assessment of normal myelination in infantile brain

Background: Myelination is a dynamic process starting during fetal life and proceeds predominantly after birth in a well-defined, predetermined manner. MR techniques such as diffusion-weighted images and the measurement of the apparent diffusion coefficient (ADC) have been applied to the study of normal brain development. Aim of the work: To demonstrate the role of Diffusion Weighted Imaging and ADC maps in assessing normal progression of the infantile brain myelination. Patients and methods: The present work included 30 infants with normal MRI study of the brain, normal psychomotor development and normal neurological examination. Conventional MRI, DWI and ADC maps were done for all the infants, the average ADC values were calculated in selected areas in white matter. Results: The age of studied children ranged from 1 month to 3 years, 13 males (43.3%) and 17 females (56.7%). In each of the selected areas of the white matter of the brain, examined ADC showed the highest values at birth and there was a significant decrease with age (p < 0.05). Conclusion: ADC values decrease with progressive increase of age. Using ADC values is useful in assessment of normal myelination development in the infantile brain and matches the results of conventional MRI

DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation

Molecular Technology and Informatics for Personalised Medicine and Healt

A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids.

Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups

Publisher Correction

The original version of this Article contained an error in the spelling of the author Min-A Jhun which was incorrectly given as Mina-A Jhun. This has now been corrected in both the PDF and HTML versions of the Article.</p