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Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges – published online 14/02/2023

Yuan graphical abstract

Shuai Yuan, Jordi Merino, Susanna C. Larsson

Exploration of causal factors underlying diabetes is of great importance not only for the development of more effective prevention strategies but also to provide insight into the molecular processes underlying disease risk. Mendelian randomisation is an epidemiological method that can strengthen causal inference based on the use of genetic variation. In this issue, Yuan et al ( summarise the evidence on potential causal risk factors for diabetes by integrating published Mendelian randomisation studies on type 1 and 2 diabetes, and reflect on future perspectives of Mendelian randomisation studies on diabetes. The authors highlight that, despite the influence of genetics on type 1 diabetes, few Mendelian randomisation studies have been conducted to identify causal exposures or molecular processes leading to increased disease risk. For type 2 diabetes, Mendelian randomisation analyses support causal associations of somatic, mental and lifestyle factors with development of the disease. The authors discuss how studies on circulating protein biomarkers, metabolites and gut microbiota provide valuable data to better understand disease pathophysiology and explore potential therapeutic targets. They conclude that more Mendelian randomisation studies in multi-ancestry cohorts are needed to examine the role of different types of physical activity, dietary components, metabolites, protein biomarkers and gut microbiome in diabetes development The figure from this review is available as a downloadable slide.

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