HDRUK Oxford Monthly Community Meeting
HDRUK Oxford Monthly Community Meeting, Monday 20 January 2025, 2:00 pm – 3:00 pm

Speaker(s): Dr. Lazaros Belbasis and Alexander Tinworth

Time: 14:00 – 15:00
Mode: Hybrid
o In-person Venue – Richard Doll Building, Lecture theatre
o To attend online – please register (link below)

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1. Speaker: Dr. Lazaros Belbasis, Oxford Population Health, University of Oxford

Title: Proteome-wide Mendelian randomization analysis highlights proteins involved into the pathogenesis of Alzheimer’s disease

Bio: Dr. Lazaros Belbasis is currently an Oxford BHF CRE Intermediate Transition Research Fellow at the Nuffield Department of Population Health (NDPH). His research focuses on the integration of multi–omics data to identify biological mechanisms and potential therapeutic targets for brain diseases. Prior joining the NDPH, Lazaros trained as a General Practitioner in Greece and undertook a PhD in the epidemiology of neurodegenerative diseases. He joined the Nuffield Department of Population Health after receiving an NDPH Early Career Research Fellowship.

Abstract: Proteins play a key role in a range of biological processes, and their dysregulation can lead to the development of diseases. High-throughput technologies have allowed the measurement of thousands of proteins in population biobanks. We aimed to identify proteins related to Alzheimer’s disease (AD) by leveraging large-scale genetic and proteomic data. We used Mendelian randomisation to test the association of 3,610 proteins with risk of AD. 78 of them were statistically significant at 5% false discovery rate with 27 of them having additional support from Bayesian co-localization. Notably, 8 out of 27 protein–disease associations (PRSS8, C1S, C1R, SIRPA, SIGLEC9, ZBTB16, PLOD2, and CLN5) corresponded to genetic loci not previously reported by GWAS for AD. The newly-associated proteins indicated the involvement of complement, microglia, and lysosomes in AD.

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2. Speaker: Alexander Tinworth, Oxford Population Health, University of Oxford

Title: GDF15 and its receptors as pathways mediating smoking related weight change

Bio: After completing his BSc in Biomedical Sciences in 2022, Alex arrived in Oxford to complete an MSc in Global Health Science and Epidemiology. It was here he learned of the expansive data collected on the human plasma proteome in individuals from both the UK Biobank and the China Kadoorie Biobank, and proposed, after completion of his MSc, to undertake a DPhil in Population Health in investigating plasma proteomic associations with cardiovascular diseases in diverse populations. Early on in his DPhil journey, he became interested in the protein, GDF15, which will form the basis of his thesis as he explores its associations in observational and genetic settings with various diseases and traits, including smoking.

Abstract: Smokers have lower body weight while smoking cessation results in weight gain through mechanisms that are not fully understood. Plasma levels of GDF15, a stress-responsive protein, and its two receptors (RET, GFRAL), measured in 3936 Chinese adults (mean BMI 24.0kg/m2), using Olink and SomaScan platforms, were tested for associations with smoking and adiposity. Smokers had lower BMI, WC, HC, WHR and BF% levels than never-smokers. Smoking was positively associated with GDF15 and with GDF15/receptor ratios in both platforms. In two-sample MR analyses, daily smoking was positively associated with higher GDF15 levels. SomaScan_GDF15 partially mediated the associations of smoking with all adiposity measures, while Olink_GDF15 mediated associations with BF%. The GDF15/RET ratio explained a higher proportion of the smoking-adiposity association than GDF15 alone in both platforms. The findings suggest that GDF15 may mediate smoking-related weight change, and could be a therapeutic target to facilitate smoking cessation and minimise cessation-induced weight gain
Date: 20 January 2025, 2:00
Venue: Richard Doll Building, Old Road Campus OX3 7LF
Venue Details: Lecture theatre
Speakers: Alexander Tinworth (University of Oxford), Dr. Lazaros Belbasis (University of Oxford)
Organising department: Big Data Institute (NDPH)
Organiser: Sumeeta Maheshwari (University of Oxford)
Organiser contact email address: hdroxford@bdi.ox.ac.uk
Host: Professor Cornelia van Duijn (University of Oxford)
Booking required?: Required
Booking url: https://events.teams.microsoft.com/event/0bacf8dc-683f-49a8-847d-02798a44041b@cc95de1b-97f5-4f93-b4ba-fe68b852cf91
Booking email: hdroxford@bdi.ox.ac.uk
Audience: Public
Editor: Sumeeta Maheshwari