Characterizing the Effect of Adiposity on Cardiometabolic Traits and the Circulating Proteome in Qatar Biobank

Lucy J Goudswaard, Shaza Zaghlool, Gaurav Thareja, Laura J Corbin, David A Hughes, Matthew Lee, Karsten Suhre, Nicholas John Timpson

Research output: Contribution to conferenceConference Posterpeer-review

Abstract

Background: The Qatari population have a high prevalence of obesity (40%). Obesity, defined by a body mass index (BMI) >30kg/m², increases the risk of various diseases such as cardiovascular disease and several cancers. We aimed to characterise the causal effect of adiposity on cardiometabolic traits and circulating proteins in the Qatar biobank (QBB). Methods: We used data from 2,935 QBB participants and performed (1) an observational analysis and (2) one sample Mendelian Randomization (MR) to estimate the effect of BMI on cardiometabolic traits and on 1,305 proteins measured by SomaLogic. MR analyses were performed by deriving a genetic risk score for BMI using 656 variants associated with BMI at p<5x10-⁸ and using this as an instrumental variable in a two-stage least squares analysis. Next, we compared effects with a cohort of European ancestry (N=2737) to determine evidence of ancestry-specific or shared proteomic effects. Results: BMI was associated with >500 proteins observationally. The MR analysis gave evidence for a causal effect of BMI on 14 proteins (after Bonferroni-correction), with higher BMI corresponding to higher levels of fatty acidbinding protein 3 (FABP3), leptin and fibrinogen, and lower levels of neural cell adhesion molecule-1 (NCAM1) and brevican core protein (BCAN). Observational effect estimates across the European and Arab populations were positively correlated (R²=0.47, p=3.0x10-¹⁸³), however FABP3 was only associated with BMI in QBB. MR results were less precise but were still positively associated across ancestries. Conclusions: We provide evidence that BMI effects proteins involved in haemostasis (fibrinogen), immune cell interaction (NCAM1) and neuronal development (NCAM1, BCAN) in an Arab population. Observational estimates suggested shared proteomic effects of BMI across European and Arab ancestries. Higher powered MR studies are required to compare causal effect estimates. Future analyses will incorporate dual-energy X-ray absorptiometry data to explore the effect of regional fat distribution on circulating proteins.
Original languageEnglish
Publication statusPublished - 17 Sept 2023
EventHuman Proteome Organization World Congress - Busan, Korea, Democratic People's Republic of
Duration: 17 Sept 202321 Nov 2023

Conference

ConferenceHuman Proteome Organization World Congress
Country/TerritoryKorea, Democratic People's Republic of
CityBusan
Period17/09/2321/11/23

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