Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci

Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10(-3)), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10(-4)). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10(-4)) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other

Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of much debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. VWF laboratory testing and full length VWF gene sequencing were performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the ISTH Bleeding Assessment Tool. At study entry, 64% of subjects had VWF:Ag or VWF:RCo below the lower limit of normal, while 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag < 30 IU/dL (82%) while subjects with type 1 VWD and VWF:Ag ≥ 30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls at 14% of subjects. All subjects with severe type 1 VWD and VWF:Ag ≤ 5 IU/dL had an abnormal bleeding score, but otherwise bleeding score did not correlate with VWF:Ag level. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal bleeding scores compared to subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population

The SPTPoL extended cluster survey

We describe the observations and resultant galaxy cluster catalog from the 2770 deg2 SPTpol Extended Cluster Survey (SPT-ECS). Clusters are identified via the Sunyaev-Zel'dovich (SZ) effect and confirmed with a combination of archival and targeted follow-up data, making particular use of data from the Dark Energy Survey (DES). With incomplete follow-up we have confirmed as clusters 244 of 266 candidates at a detection significance ξ ≥ 5 and an additional 204 systems at 4 4 threshold, and 10% of their measured SZ flux. We associate SZ-selected clusters, from both SPT-ECS and the SPT-SZ survey, with clusters from the DES redMaPPer sample, and we find an offset distribution between the SZ center and central galaxy in general agreement with previous work, though with a larger fraction of clusters with significant offsets. Adopting a fixed Planck-like cosmology, we measure the optical richness-SZ mass (l - M) relation and find it to be 28% shallower than that from a weak-lensing analysis of the DES data-a difference significant at the 4σ level-with the relations intersecting at λ = 60. The SPT-ECS cluster sample will be particularly useful for studying the evolution of massive clusters and, in combination with DES lensing observations and the SPT-SZ cluster sample, will be an important component of future cosmological analyses

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

TRY plant trait database – enhanced coverage and open access

Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Detection of CMB-cluster lensing using polarization data from SPTpol

We report the first detection of gravitational lensing due to galaxy clusters using only the polarization of the cosmic microwave background (CMB). The lensing signal is obtained using a new estimator that extracts the lensing dipole signature from stacked images formed by rotating the cluster-centered Stokes Q U map cutouts along the direction of the locally measured background CMB polarization gradient. Using data from the SPTpol 500     deg 2 survey at the locations of roughly 18 000 clusters with richness λ ≥ 10 from the Dark Energy Survey (DES) Year-3 full galaxy cluster catalog, we detect lensing at 4.8 σ . The mean stacked mass of the selected sample is found to be ( 1.43 ± 0.40 ) × 10 14 M ⊙ which is in good agreement with optical weak lensing based estimates using DES data and CMB-lensing based estimates using SPTpol temperature data. This measurement is a key first step for cluster cosmology with future low-noise CMB surveys, like CMB-S4, for which CMB polarization will be the primary channel for cluster lensing measurements

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

The Telychian (early Silurian) oxygenation event in northern Europe:A geochemical and magnetic perspective

Widespread marine red beds in the European Telychian (lower-Silurian) are one expression of an interval of unusually widespread oxic conditions in low palaeolatitude Silurian seas. This work examines in detail the geochemical and magnetic susceptibility record of cores from southern Poland, which also express the Telychian oxygenation event in grey-mudstones. The geochemical data provide an evaluation of redox conditions, palaeoweathering, sediment provenance, primary palaeoproductivity and upwelling. Sediment provenance is evaluated against possible sources on the East European Craton. The data suggest that the magnetic susceptibility is carried by both paramagnetic Fe-silicates and Fe-oxides. Magnetic data are supplemented by magnetic hysteresis and isothermal remanent magnetisations, and mineralogical data on selected samples. In Poland the oxygenation event is clearly expressed in larger Fe2O3 and magnetic susceptibility, caused by enhanced palaeoweathering, changes in sediment provenance and a redox influence on the preservation of Fe-oxides. A much briefer oxygenation event is detected in the upper Rhuddanian. Palaeoproductivity fluxes indicate that the Telychian oxygenation event was caused by a reduction in primary oceanic palaeoproductivity, possibly linked to a reduction in nutrient delivery to the margin of the East European Craton, inferred to be caused by increased aridity. The increased aridity stimulated enhanced delivery of Fe-enriched aeolian dust from soils, generating a magnetic susceptibility and Fe2O3 expression of the Telychian oxygenation event

Geomagnetic polarity during the early Silurian:The first magnetostratigraphy of the Llandovery

Magnetostratigraphic studies in the Silurian are absent, and what is understood about the geomagnetic polarity during this time is based on polarity bias-type data from palaeopole-type studies. We provide the first composite magnetic polarity record through the Lower Silurian (Llandovery) from the magnetostratigraphy of six sections. These are integrated with graptolite biostratigraphy and some carbon isotope chemostratigraphy. The palaeomagnetic signal is carried by both haematite and magnetite, with haematite dominating in red-coloured mudstones and mostly magnetite in non-red lithologies. The influence of possible tectonic disruption of the fabric is assessed using anisotropy of magnetic susceptibility. Only the most thermally mature section at Backside Beck shows the imprint of initial tectonic fabric formation. The Llandovery is divided into 6 major normal-reverse-polarity chron couplets (referred to as LL1 to LL6). An additional longer, exclusively normal polarity interval (referred to as WE1n), beginning in Telychian Stage slice Te3, runs into the lower Sheinwoodian. Within these five polarity couplets there are 10 further submagnetozones, and 10 tentative submagnetozones. Average reversal frequency (including the tentative submagnetozones) was ca. 3.0 Myr−1 in the Early Silurian, which is probably an underestimate, due to insufficient sampling density in some parts of the Rhuddanian and Aeronian. This reversal frequency is similar to that in the late Cenozoic, indicating the future potential utility of magnetostratigraphy for high-resolution correlation and dating in the Early Silurian