DHEA and response to antidepressant treatment: A Mendelian Randomization analysis.

Treatment response is hard to predict and detailed mechanisms unknown. Lower levels of the dehydroepiandrosterone sulphate (DHEA(S)) - a precursor to testosterone and estrogen - have been associated to depression and to response to antidepressant treatment. Previous studies however may have been ridden by confounding and reverse causation. The aim of this study is to evaluate whether higher levels of DHEA(S) are causally linked to response to antidepressants using mendelian randomization (MR). We performed a Two-sample MR analysis using data the largest publicly available GWAS of DHEA(S) levels (n = 14,846) using eight common genetic variants associated to DHEA(S) (seven single nucleotide polymorphisms and one variant rs2497306) and the largest GWAS of antidepressant response (n = 5218) using various MR methods (IVW, MR Egger, Weighted mean, weighted mode, MR-PRESSO) and single SNP analysis. We further investigated for pleiotropy conducting a look up on PhenoScanner and GWAS Catalog. Results show no evidence for DHEA(S) gene risk score from any of MR methods, however, we found a significant association on individual variant analysis for rs11761538, rs17277546, and rs2497306. There was some evidence for heterogeneity and pleiotropy. This is the first paper to show some evidence for a causal association of genetically-predicted DHEA and improvement of depressive symptoms. The effect is not a simple linear effect, and we were unable to dissect whether the effect was direct effect of DHEA(S), mediated by DHEA(S) or on the pathway is not yet clear. Further studies using more refined instrumental variables will help clarify this association.

Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Assay for the Rapid Detection of African Horse Sickness Virus.

African horse sickness (AHS) is a disease of equids caused by African Horse Sickness Virus (AHSV) and is transmitted by Culicoides midges. AHS is endemic in sub-Saharan Africa, but during the past century, outbreaks of significant economic importance and elevated mortality have been recorded in Northern African countries, the Iberian and Arabian Peninsula, the Middle East and the Indian subcontinent. Effective control combines the application of early warning systems, accurate laboratory diagnosis and reporting, animal movement restrictions, suitable vaccination and surveillance programs, and the coordination of all these measures by efficient veterinary services. Conventional reverse-transcriptase (RT) PCR (RT-PCR) and real-time RT-PCR (rRT-PCR) assays have improved the sensitivity and rapidity of diagnosing AHS, resulting in the adoption of these methods as recommended tests by the World Organisation for Animal Health (OIE). However, currently these assays are only performed within laboratory settings; therefore, the development of field diagnostics for AHS would improve the fast implementation of control policies. Loop-mediated isothermal amplification (LAMP) is an isothermal, autocycling, strand-displacement nucleic acid amplification technique which can be performed in the field. LAMP assays are attractive molecular assays because they are simple to use, rapid, portable and have sensitivity and specificity within the range of rRT-PCR. This study describes the development of a novel RT-LAMP assay for the detection of AHSV. The AHSV RT-LAMP assay has an analytical sensitivity of 96.1% when considering an rRT-PCR cut-off value of CT  > 36, or 91.3% when no rRT-PCR cut-off is applied. Diagnostic sensitivity and specificity were 100%. This assay provides for a rapid and low cost AHS diagnostic for use in the field.

Uromodulin gene variants and their association with renal function and blood pressure in cats: a pilot study.

OBJECTIVES: In humans, genome-wide association studies have identified variants in the uromodulin gene (UMOD) associated with blood pressure and renal function. This study aimed to evaluate the association of single nucleotide polymorphisms at the UMOD locus with renal function and blood pressure in cats. METHODS: We retrospectively identified cats aged 14 years that had participated in a geriatric monitoring program, and from which stored DNA samples were available, from a computerised database. We then measured the association of specific single nucleotide polymorphisms in the feline UMOD gene with renal function and systolic blood pressure as continuous variables and, also, the dichotomous outcome of azotaemic chronic kidney disease and systemic hypertension. RESULTS: Eight intronic single nucleotide polymorphisms, one 1372 base pairs upstream from UMOD and two exonic single nucleotide polymorphisms were evaluated in 227 cats with renal and blood pressure data. An analysis of 188 cats found four single nucleotide polymorphisms to be significantly associated (P<0·01) with systolic blood pressure although all were in linkage disequilibrium. No significant associations were identified between single nucleotide polymorphisms and renal function or chronic kidney disease. CLINICAL SIGNIFICANCE: Results of this pilot study suggest that genetic variation in UMOD might influence blood pressure in cats, similar to findings in humans. Validation of these results is required.