Familial genetic and environmental risk profile and high blood pressure event: a prospective cohort of cardio-metabolic and genetic study

Abstract

Background and aims

High blood pressure is the heritable risk factor for cardiovascular diseases. We investigated whether the presence of familial genetic and environmental risk factors are associated with increased risk of high blood pressure.

Methods

A total of 4,559 individuals from 401 families were included in this study. Familial aggregation analysis was carried out on systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and waist circumference (WC), and heritability was estimated for SBP and DBP. The association between familial risk factors and blood pressure traits including, incidence of hypertension, SBP and DBP was estimated separately using regression-based two-level Haseman-Elston (HE) method, with individual and familial BMI and WC as environmental exposures and familial genetic profile of known variants as genetic risk factors in 210 index families (≥2 hypertensive cases). Models were adjusted for the two nested sets of covariates.

Results

During a follow-up of 15 years, the SBP, DBP, BMI and WC were highly correlated in inter class of mother-offspring and intraclass of sister-sister with heritability of 30 and 25% for DBP and SBP, respectively. Among index families, those whose members with higher familial BMI or WC had significantly increased risk of hypertension and consistent, strong signals of rs2493134 (AGT) linked with SBP and DBP, rs976683 (NLGN1) linked with SBP and HTN, and epistasis of rs2021783 (TNXB) and known genetic variants linked with all blood pressure traits.

Conclusions

Findings from this study show that familial genetic and environmental risk profile increase risk for high blood pressure beyond the effect of the individuals’ own risk factors.

Keywords:

• Hypertension
• blood pressure
• familial aggregation
• genetics
• linkage
• epistasis

Acknowledgment

We are grateful to all TLGS and Gemiran colleagues that assisted with this study through the data collection process.

Author contributions

GK, SS and MA had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis; GK, MSD, SS, and MA contributed to study concept, design, and supervision; MSD, BSK, KG, MA, AZ and GK contributed in acquisition of data; GK, MSD, MA, SS, NKH and MAR contributed in analysis and interpretation of data; GK, MSD, MA, SS, AZ and SR contributed in statistical analysis; FA, MSD, and FH contributed in administrative, technical, or material support; GK, MSD, NKH, FG, MA, AZ and SS: drafting of the manuscript, English language editing and critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study has been funded by [grant number of 21083] from the Deputy for Research Affairs of SBMU.