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Objectives: The aim of this study is to explore the contribution of genetically driven cardiometabolic risk factors for development of carotid arterial thickening in patients with type 2 diabetes., Methods: In total, 12 genetic risk scores for blood pressure, blood lipids and glycaemic traits were constructed. The genetic risk scores were tested for association with carotid intima-media thickness and plaques in patients with type 2 diabetes ( n = 401) and in non-diabetic individuals ( n = 648) and for association with glucose levels in two population-based cohorts ( n = 1328 and n = 6161)., Results: In patients with type 2 diabetes, the genetic risk scores for pulse pressure were positively associated with plaque formation ( β = 0.036 ± 0.01 standard deviation/allele, p = 0.003). The genetic risk score for diastolic blood pressure was negatively associated with carotid intima-media thickness ( β = -0.037 ± 0.01 standard deviation/allele, p = 0.005), although not significant after correction for multiple testing ( p < 0.0042). In a meta-analysis of individuals with and without type 2 diabetes, the high-density lipoprotein genetic risk scores showed a trend towards an inverse association with carotid intima-media thickness and plaques, while the low-density lipoprotein genetic risk scores showed a trend towards a positive association with plaque formation but did reach the statistical threshold., Conclusion: Genetic loci for pulse pressure are associated with plaque formation among patients with type 2 diabetes, suggesting an underlying genetic contribution to arterial stiffening and atherosclerosis.

Background: Recent GWAS studies have identified more than 300 SNPs associated with variation in blood pressure. We investigated whether a genetic risk score constructed from these variants is associated with burden of coronary heart disease., Methods: From 2010-2014, 4,809 individuals admitted to coronary angiography in Capital Region of Copenhagen were genotyped. We calculated hypertension GRS comprised of GWAS identified SNPs associated with blood pressure. We performed logistic regression analyses to estimate the risk of hypertension and prevalent CHD. We also assessed the severity of CHD associated with the GRS. The analyses were performed using GRS quartiles. We used the Inter99 cohort to validate our results and to investigate for possible pleiotropy for the GRS with other CHD risk factors., Results: In COGEN, adjusted odds ratios comparing the 2nd, 3rd and 4th cumulative GRS quartiles with the reference were 1.12(95% CI 0.95-1.33), 1.35(95% CI 1.14-1.59) and 1.29(95% CI 1.09-1.53) respectively, for prevalent CHD. The adjusted multinomial logistic regression showed that 3rd and 4th GRS quartiles were associated with increased odds of developing two(OR 1.33, 95% CI 1.04-1.71 and OR 1.36, 95% CI 1.06-1.75, respectively) and three coronary vessel disease(OR 1.77, 95% CI 1.36-2.30 and OR 1.65, 95% CI 1.26-2.15, respectively). Similar results for incident CHD were observed in the Inter99 cohort. The hypertension GRS did not associate with type 2 diabetes, smoking, BMI or hyperlipidemia., Conclusion: Hypertension GRS quartiles were associated with an increased risk of hypertension, prevalent CHD, and burden of coronary vessel disease in a dose-response pattern. We showed no evidence for pleiotropy with other risk factors for CHD., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: The Novo Nordisk Foundation Center for Basic Metabolic Research performed genotyping, quality control of the genotypes and genotype imputation. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

In the Ethics subsection of the Methods, there is an error in the paragraph. Reference 1 Lukács Krogager M, Skals RK, Appel EVR, Schnurr TM, Engelbrechtsen L, Have CT, et al. (2018) Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography. [Extracted from the article]