The Roles of Genetic and Early-Life Environmental Factors in the Association Between Overweight or Obesity and Hypertension: A Population-Based Twin Study

Abstract

Aims/HypothesisWe aimed to explore whether and to what extent overweight or obesity could increase the risk of hypertension, and further to estimate the roles of genetic and early-life familial environmental factors in their association.MethodsThis prospective twin study was based on the Chinese National Twin Registry (CNTR), which collected information from self-report questionnaires. We conducted unmatched case-control analysis to examine the association between overweight or obesity and hypertension. And further to explore whether genetics and familiar environments shared within a twin pair, accounted for their association via co-twin matched case-control design. Generalized estimating equation (GEE) models and conditional logistic regressions were used in the unmatched and matched analyses, respectively. Then, we used logistic regressions to test the difference in odds ratios (ORs) between the unmatched and matched analyses. Finally, through bivariate twin model, the roles of genetic and environmental factors in the body mass index (BMI)- hypertension association were estimated.ResultsOverall, we included a total of 30,617 twin individuals, of which 7533 (24.6%) twin participants were overweight or obesity and 757 (2.5%) developed hypertension during a median follow-up time of 4.4 years. In the GEE model, overweight or obesity was associated with a 94% increased risk of hypertension (OR=1.94, 95% confidence interval (CI): 1.64~2.30). In the conditional logistic regression, the multi-adjusted OR was 1.80 (95% CI: 1.18~2.74). The difference in OR between unmatched and matched analyses was significant (P=0.016). Specifically, overweight or obesity was not associated with hypertension risk in the co-twin design when we full controlled genetic and familiar environmental factors (OR=0.89, 95 CI: 0.46~1.72). After controlling for age and sex, we found the positive BMI-hypertension association was mainly explained by a genetic correlation between them (rA= 0.59, 95% CI: 0.44~1.00).Conclusions/InterpretationGenetics and early-life environments shared by participants within a twin pair appear to account for the association between overweight or obesity and hypertension risk.

Hypertension Related to Obesity: Pathogenesis, Characteristics and Factors for Control

“…A recent population-based study on 30,617 twin individuals showed that being overweight or obese was associated with a 94% increased risk of hypertension (OR = 1.94, 95% CI: 1.64~2.30). After controlling for all other variables, this association was mainly explained by genetics [ 38 ]. However, there is still no consensus on which specific genes have a direct role in both obesity and hypertension.…”

“…However, more recent studies have not been able to verify those results. A replication study by Goulet et al was done on a similar sample population and using similar methods as the study by Melka et al Their results showed that rs9930333 ( FTO ) was associated with increased body mass index, but not with increased systolic blood pressure [ 38 ]. A cross-sectional study also found no significant difference in genotypic frequencies of FTO rs9939609 SNP between hypertensive patients and healthy controls [ 42 ].…”

Impact of maternal gestational weight gain in twin pregnancies on early childhood obesity risk: A longitudinal birth cohort study

“…We estimated the linear effect between total GWG or trimester GWGRs and age-specific BAZ by using a generalized estimation equation (GEE) model and the non-linear effect by using a restricted cubic spline (RCS) linear regression model. The GEE model is a regression method that extends the generalized linear model to adjust for the correlation between a set of twins, which is commonly used in twin studies (28)(29)(30). The 5, 35, 65, and 95th percentiles of the distribution of specific trimester GWGRs were used in the RCS model.…”

Appraisal of Gene-Environment Interactions in GWAS for Evidence-Based Precision Nutrition Implementation

“…A recent review suggests that the application of information from obesity-related GWAS data can help shed light on the etiological mechanism of obesity-related metabolic risk [ 56 ]. Furthermore, a recent study carried out on twins showed that environmental factors such as smoking status, alcohol consumption and physical activity are key triggers in the development of obesity-associated hypertension [ 57 ], and a previous meta-analysis suggested that this association may be mediated by a SNP at the FTO locus [ 58 ]. Similarly, another GWAS also showed evidence linking alcohol intake with blood pressure through genes previously associated with alcohol intake, such as PINX1 , GATA4 , BLK , FTO and GABBR2 [ 50 ].…”