Diabetes genetic score, diabetes, and arterial stiffness: a Mendelian randomisation analysis in Chinese

Abstract Background The nature and underlying mechanisms of the association between type 2 diabetes and the risk of increased arterial stiffness are unclear. We aimed to study this association using the Mendelian randomisation approach. Methods We did a Mendelian randomisation analysis in 11 385 participants, aged 40 years or more, recruited from two communities in Baoshan district, Shanghai, China, in 2011–13. We genotyped 34 common variants associated with type 2 diabetes that had previously been identified and validated in east Asians, and created the type 2 diabetes genetic risk score. Arterial stiffness was assessed non-invasively with measurement of brachial-ankle pulse wave velocity (baPWV). The effect of type 2 diabetes on the increased risk of arterial stiffness was quantified by instrumental variable estimator. The institutional review board of Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, approved the study protocol. All participants gave written informed consent. Findings We found that each ten-point increase in the genetic risk score was associated with a 1·39 times increment in type 2 diabetes risk and an odds ratio (OR) for increased arterial stiffness of 1·21 (95% CI 1·06–1·38). Compared with the lowest quartile of the genetic risk score, the highest quartile was associated with a 1·22 (95% CI 1·06–1·40) times increment risk of increased arterial stiffness. Linear regression adjusted for age, sex, and body-mass index showed that every ten-point increase of the genetic risk score was associated with a rise in baPWV by 36·71 cm/s (p