Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality. To advance our understanding of the biology contributing to VTE, we conducted a genome-wide association study (GWAS) of VTE and a transcriptome-wide association study (TWAS) based on imputed gene expression from whole blood and liver. We meta-analyzed GWAS data from 18 studies for 30 234 VTE cases and 172 122 controls and assessed the association between 12 923 718 genetic variants and VTE. We generated variant prediction scores of gene expression from whole blood and liver tissue and assessed them for association with VTE. Mendelian randomization analyses were conducted for traits genetically associated with novel VTE loci. We identified 34 independent genetic signals for VTE risk from GWAS meta-analysis, of which 14 are newly reported associations. This included 11 newly associated genetic loci (C1orf198, PLEK, OSMR-AS1, NUGGC/SCARA5, GRK5, MPHOSPH9, ARID4A, PLCG2, SMG6, EIF5A, and STX10) of which 6 replicated, and 3 new independent signals in 3 known genes. Further, TWAS identified 5 additional genetic loci with imputed gene expression levels differing between cases and controls in whole blood (SH2B3, SPSB1, RP11-747H7.3, RP4-737E23.2) and in liver (ERAP1). At some GWAS loci, we found suggestive evidence that the VTE association signal for novel and previously known regions colocalized with expression quantitative trait locus signals. Mendelian randomization analyses suggested that blood traits may contribute to the underlying risk of VTE. To conclude, we identified 16 novel susceptibility loci for VTE; for some loci, the association signals are likely mediated through gene expression of nearby genes.

Fatal skull trauma in caged layer chickens associated with a moving feed hopper: diagnosis based on autopsy examination, forensic computed tomography and farm visit.

Investigation of unexpected mortality in caged layer chickens led to the discovery of a consistent traumatic injury to the heads of affected hens. Initial post-mortem examination found linear skin lacerations and associated fractures in the dorsal cranium of all birds examined, and 5 to 10 mm deep trauma in the underlying brain tissue. Post-mortem multidetector computed tomography (CT) scanning of two affected birds demonstrated similar obliquely orientated, linear, depressed fractures of the skulls consistent with a single, severe impact force to the head. Both skull fractures had a pattern of rounded, rostral expansion measuring approximately 3 mm in width. On inspection of the cages during a farm visit, this CT pattern corresponded with the size and shape of sheet metal lugs holding feed troughs onto the cages (on which blood stains were subsequently observed). Based on this analysis and hypothesizing that hunger was a triggering factor, a recommendation was made to reverse the shed "lights on" and feed hopper operation times with instant reduction in mortality. This case highlights the value of post-mortem CT imaging in bird death investigation where trauma is a postulated cause.

Platelet function as a risk factor for venous thromboembolism in the Framingham Heart Study.

INTRODUCTION: The relationship of venous thromboembolism (VTE) with platelet reactivity is unclear. Platelet function plays a key role in arterial thrombosis. Evidence suggests antiplatelet agents also effects in reducing VTE. Our aim is to describe the role of baseline platelet function in development of VTE in the community-based Framingham Heart Study (FHS) cohort. MATERIALS AND METHODS: Participants in the Framingham Offspring cohort fifth examination and Omni cohort first examination were eligible. We used light transmission aggregometry to measure platelet aggregation in response to collagen and a range of ADP and epinephrine doses. The study population consisted of 2831 participants [average age 54.3years; 57% female]. RESULTS AND CONCLUSIONS: During a median follow-up of 20.4years, we observed 138 incident VTE events. In age-, sex- and cohort-adjusted analysis an increase in collagen lag time was associated with increased risk for incident VTE (HR 1.01 [1.00-1.02]; p=0.049). Increased maximal aggregation to low dose epinephrine (1.0µM) was associated with lower VTE risk (HR 0.84 [0.71-0.99]; p=0.042]). However, additional multivariable analyses attenuated the collagen-VTE and epinephrine-VTE associations to trends, primarily due to adjustment for baseline body mass index (BMI), a VTE risk factor and potential modifier of platelet function. Secondary analyses considering varying follow-up periods, cancer incidence and interim aspirin use did not dramatically affect the collagen and epinephrine trends observed. Baseline platelet aggregability was only weakly associated with incident VTE, and in a paradoxical direction, in a community-based population. Other markers of platelet function and hemostasis could prove to be more useful predictors.