Biology subjects

Cuzick, J.

Publications and source records attributed to Cuzick, J..

2 recordsLinked to original sources

bioRxiv2019

The Parkinsons Disease Mendelian Randomization Research Portal

BackgroundMendelian randomization (MR) is a method for exploring observational associations to find evidence of causality.\n\nObjectiveTo apply MR between multiple risk factors/phenotypic traits (exposures) and Parkinsons disease (PD) in a large, unbiased manner, and to create a public resource for research.\n\nMethodsWe used two-sample MR in which the summary statistics relating to SNPs from genome wide association studies (GWASes) of 5,839 exposures curated on MR Base were used to assess causal relationships with PD. We selected the highest quality exposure GWASes for this report (n=401). For the disease outcome, summary statistics from the largest published PD GWAS were used. For each exposure, the causal effect on PD was assessed using the inverse variance weighted (IVW) method, followed by a range of sensitivity analyses. We used a false discovery rate (FDR) corrected p-value of <0.05 from the IVW analysis to prioritize traits of interest.\n\nResultsWe observed evidence for causal associations between twelve exposures and risk of PD. Of these, nine were causal effects related to increasing adiposity and decreasing risk of PD. The remaining top exposures that affected PD risk were tea drinking, time spent watching television and forced vital capacity, but the latter two appeared to be biased by violations of underlying MR assumptions.\n\nDiscussionWe present a new platform which offers MR analyses for a total of 5,839 GWASes versus the largest PD GWASes available (https://pdgenetics.shinyapps.io/pdgenetics/). Alongside, we report further evidence to support a causal role for adiposity on lowering the risk of PD.

neuroscience↗

bioRxiv2018

Screening performance of abbreviated versions of the UPSIT smell test

BackgroundHyposmia features in several neurodegenerative conditions, including Parkinsons disease (PD). The University of Pennsylvania Smell Identification Test (UPSIT) is a widely used screening tool for detecting hyposmia, but is time-consuming and expensive when used on a large scale.\n\nMethodsWe assessed shorter subsets of UPSIT items for their ability to detect hyposmia in 891 healthy participants from the PREDICT-PD study. Established shorter tests included Versions A and B of both the 4-item Pocket Smell Test (PST) and 12-item Brief Smell Identification Test (BSIT). Using a data-driven approach, we evaluated screening performances of 23,231,378 combinations of 1-7 smell items from the full UPSIT.\n\nResultsPST Versions A and B achieved sensitivity/specificity of 76.8%/64.9% and 86.6%/45.9% respectively, whilst BSIT Versions A and B achieved 83.1%/79.5% and 96.5%/51.8% for detecting hyposmia defined by the longer UPSIT. From the data-driven analysis, two optimised sets of 7 smells surpassed the screening performance of the 12 item BSITs (with validation sensitivity/specificities of 88.2%/85.4% and 100%/53.5%). A set of 4 smells (Menthol, Clove, Gingerbread and Orange) had higher sensitivity for hyposmia than PST-A, -B and even BSIT-A (with validation sensitivity 91.2%). The same 4 smells also featured amongst those most commonly misidentified by 44 individuals with PD compared to 891 PREDICT-PD controls and a screening test using these 4 smells would have identified all hyposmic patients with PD.\n\nConclusionUsing abbreviated smell tests could provide a cost-effective means of screening for hyposmia in large cohorts, allowing more targeted administration of the UPSIT or similar smell tests.

neuroscience↗