Combining evidence from human genetic and functional screens to identify pathways altering obesity and fat distribution.

Overall adiposity and body fat distribution are heritable traits associated with altered risk of cardiometabolic disease and mortality. Performing rare-variant (minor allele frequency <1%) association testing using exome-sequencing data from 402,375 participants of European ancestry in the UK Biobank for nine overall and tissue-specific fat distribution traits, we identified 19 genes where putatively damaging rare variation associated with at least one trait (Bonferroni-adjusted p < 1.58 × 10) and 50 additional genes at false discovery rate (FDR) ≤1% (p ≤ 4.

Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.

Genome-wide association studies (GWASs) may help inform the etiology of infertility. Here, we perform GWAS meta-analyses across seven cohorts in up to 42,629 cases and 740,619 controls and identify 25 genetic risk loci for male and female infertility. We additionally identify up to 269 genetic loci associated with follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone through sex-specific GWAS meta-analyses (n = 6,095-246,862).

Combining evidence from human genetic and functional screens to identify pathways altering obesity and fat distribution.

Overall adiposity and body fat distribution are heritable traits associated with altered risk of cardiometabolic disease and mortality. Performing rare variant (minor allele frequency<1%) association testing using exome-sequencing data from 402,375 participants in the UK Biobank (UKB) for nine overall and tissue-specific fat distribution traits, we identified 19 genes where putatively damaging rare variation associated with at least one trait (Bonferroni-adjusted <1.58×10 ) and 50 additional genes at FDR≤1% ( ≤4.

Characterising the genetic architecture of changes in adiposity during adulthood using electronic health records.

Obesity is a heritable disease, characterised by excess adiposity that is measured by body mass index (BMI). While over 1,000 genetic loci are associated with BMI, less is known about the genetic contribution to adiposity trajectories over adulthood. We derive adiposity-change phenotypes from 24.

Exome-wide evidence of compound heterozygous effects across common phenotypes in the UK Biobank.

The phenotypic impact of compound heterozygous (CH) variation has not been investigated at the population scale. We phased rare variants (MAF ∼0.001%) in the UK Biobank (UKBB) exome-sequencing data to characterize recessive effects in 175,587 individuals across 311 common diseases.

Exome-wide evidence of compound heterozygous effects across common phenotypes in the UK Biobank.

Exome-sequencing association studies have successfully linked rare protein-coding variation to risk of thousands of diseases. However, the relationship between rare deleterious compound heterozygous (CH) variation and their phenotypic impact has not been fully investigated. Here, we leverage advances in statistical phasing to accurately phase rare variants (MAF ~ 0.

The genetic architecture of changes in adiposity during adulthood.

Obesity is a heritable disease, characterised by excess adiposity that is measured by body mass index (BMI). While over 1,000 genetic loci are associated with BMI, less is known about the genetic contribution to adiposity trajectories over adulthood. We derive adiposity-change phenotypes from 1.

Correction: Obesity and risk of female reproductive conditions: A Mendelian randomisation study.

[This corrects the article DOI: 10.1371/journal.pmed.

Obesity and risk of female reproductive conditions: A Mendelian randomisation study.

Background: Obesity is observationally associated with altered risk of many female reproductive conditions. These include polycystic ovary syndrome (PCOS), abnormal uterine bleeding, endometriosis, infertility, and pregnancy-related disorders. However, the roles and mechanisms of obesity in the aetiology of reproductive disorders remain unclear.

Mitochondria and Peroxisome Remodeling across Cytomegalovirus Infection Time Viewed through the Lens of Inter-ViSTA.

Nearly all biological processes rely on the finely tuned coordination of protein interactions across cellular space and time. Accordingly, generating protein interactomes has become routine in biological studies, yet interpreting these datasets remains computationally challenging. Here, we introduce Inter-ViSTA (Interaction Visualization in Space and Time Analysis), a web-based platform that quickly builds animated protein interaction networks and automatically synthesizes information on protein abundances, functions, complexes, and subcellular localizations.

Conservation and divergence of protein pathways in the vertebrate heart.

Heart disease is the leading cause of death in the western world. Attaining a mechanistic understanding of human heart development and homeostasis and the molecular basis of associated disease states relies on the use of animal models. Here, we present the cardiac proteomes of 4 model vertebrates with dual circulatory systems: the pig (Sus scrofa), the mouse (Mus musculus), and 2 frogs (Xenopus laevis and Xenopus tropicalis).