Genetic predisposition to obesity and risk of subclinical atherosclerosis

Obesity has been associated with increased common carotid artery (CCA) intima-media thickness (IMT), a measure of subclinical atherosclerosis. We assessed the association between genetic predisposition to obesity and CCA IMT. The study included 428 young Chinese adults with CCA IMT measured using a high-resolution B-mode tomographic ultrasound system. We created a genetic risk score (GRS) by summing the risk alleles of 6 obesity-associated genetic variants confirmed in our previous analyses. The GRS was significantly associated with greater CCA IMT (p<0.001) after adjustment for age and gender. Per 2 alleles of the GRS was related to 0.023 mm increment in IMT. The association was attenuated by one half with additional adjustment for obesity status, but remained significant (p=0.009). In addition, we found that blood pressure significantly modified the association between the GRS and CCA IMT (p for interaction=0.001). The associations between the GRS and CCA IMT were stronger in participants with systolic blood pressure (SBP) ≥120 mmHg and/or diastolic blood pressure (DBP) ≥80 mmHg (per 2 allele increment of the GRS relating to 0.028 mm greater CCA IMT, p for trend<0.001) than those with SBP<120 mmHg and DBP<80 mmHg (per 2 allele increment of the GRS relating to 0.001 smaller CCA IMT, p for trend=0.930). Our data provides suggestive evidence supporting the potential causal relation between obesity and development of subclinical atherosclerosis. Elevated blood pressure might amplify the adverse effect of obesity on cardiovascular risk.