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This is the public repository for the poster presented at 2022 NIDA Virtual Genetics and Epigenetics Cross-Cutting Research Team Meeting. Contributors: MadhurBain Singh (1,2), Philip Vinh (1,2), Yi (Daniel) Zhou (2,3), Luis F.S. Castro-de-Araujo (2), Brad Verhulst (4), Conor V. Dolan (5), and Michael C. Neale (1,2,3,5) Affiliations: 1. Department of Human & Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA; 2. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA; 3. Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA; 4. Department of Psychiatry and Behavioral Sciences, Texas A&M University, College Station, TX, USA; 5. Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.

The purpose of this study was to determine the incidence of deep venous thrombosis in medical intensive care unit patients receiving deep venous thrombosis prophylaxis. This was a prospective cohort study of 141 consecutive adult patients anticipated to remain in the medical intensive care unit for >48 hours. Deep venous thrombosis prophylaxis was provided using subcutaneous unfractionated heparin or a sequential compression device according to risk-stratified protocol. Compression ultrasound was performed. Fourteen patients (9.9%) developed deep venous thrombosis on follow-up studies. Incidence of deep venous thrombosis was 7.9% per person year (95% confidence interval, 4.8-12.8). Two of 14 developed pulmonary embolism. Eight patients required full anticoagulation with intravenous heparin or coumadin. In-hospital mortality was similar in both groups. Patients with deep venous thrombosis had a statistically higher risk of pulmonary embolism: 14.2% (95% confidence interval, 2.0-43.0) versus 0.0% (95% confidence interval, 0-3; P= .009). Incidence of deep venous thrombosis is high in medical intensive care unit patients receiving standard prophylaxis. Adherence to strict deep venous thrombosis prophylaxis protocol and exploration of other prophylaxis regimens should be pursued.

Trypanosoma brucei evades its host's immune response by utilizing the system of antigenic variation, whereby the organism sequentially expresses antigenically distinct variant surface glycoproteins (VSGs). Actively expressed VSG genes are found in VSG expression sites (ESs), and transcription of these ESs is directed by a small promoter composed of two essential cis-acting elements, the VSG ES promoter upstream element (VUE) and VSG ES promoter downstream element (VDE). Using electrophoretic mobility shift assays, we have identified double-stranded DNA binding activity in bloodstream-form trypanosome nuclear extracts. This activity, the VEP complex, is specific for the VSG ES promoter, and requires the intact sequences of the VUE and VDE in the appropriate spacing. These requirements of VEP Complex formation parallel the requirements for promoter function, suggesting that the VEP complex may be composed of functionally significant trans-acting factors. Furthermore, the requirement of both elements suggests that the binding of factors to the promoter may be cooperative. However, subtly different binding characteristics were observed when we used nuclear extracts derived from procyclic trypanosomes.

Mendelian Randomization (MR) has become an important tool for causal inference in the health sciences. It takes advantage of the random segregation of alleles to control for background confounding factors. In brief, the method works by using genetic variants as instrumental variables, but it depends on the assumption of exclusion restriction, i.e., that the variants affect the outcome exclusively via the exposure variable. Equivalently, the assumption states that there is no horizontal pleiotropy from the variant to the outcome. This assumption is unlikely to hold in nature, so several extensions to MR have been developed to increase its robustness against horizontal pleiotropy, though not eliminating the problem entirely (Sanderson et al. 2022). The Direction of Causation (DoC) model, which affords information from the cross-twin cross-trait correlations to estimate causal paths, was extended with polygenic scores to explicitly model horizontal pleiotropy and a causal path (MR-DoC, Minică et al 2018). MR-DoC was further extended to accommodate bidirectional causation (MR-DoC2 ; Castro-de-Araujo et al. 2023). In the present paper, we compared the power of the DoC model, MR-DoC, and MR-DoC2. We investigated the effect of phenotypic measurement error and the effect of misspecification of unshared (individual-specific) environmental factors on the parameter estimates., Competing Interests: Declarations Conflicts of interest Authors report no conflicts of interest