New research reveals that teens with higher BMI are more likely to experience elevated blood pressure as adults, especially if they have a genetic predisposition—underscoring the need for early weight management to reduce lifelong cardiovascular risks.

Study: Body mass index modifies genetic susceptibility to high systolic blood pressure in adolescents and young adults: results from an 18-year longitudinal study. Image Credit: BELL KA PANG / Shutterstock

In a recent study published in the Journal of Human Hypertension, researchers used an extensive, long-term dataset to elucidate whether adolescent body mass index (BMI) can alter young people’s genetic predisposition to systolic blood pressure (SBP). Their dataset comprised blood (collected at age 14) and saliva (collected at ages 20 and 25) samples obtained from 714 participants (European ancestry) across different growth phases (12, 15, 17, 24, and 30 years).

Simultaneously, researchers generated two genetic risk scores (GRS) derived from genome-wide association studies (GWAS) to identify single-nucleotide polymorphisms (SNPs) associated with adult SBP. GRS182, which incorporated more SNPs than GRS22, was found to be a stronger predictor of SBP in adulthood, explaining up to 5.6% of SBP variance in females but less than 1% in males.

Linear mixed models revealed that increased BMI values (22 kg/m² to 35 kg/m²) progressively amplified associations between GRS and SBP, confirming that higher adolescent BMIs can exacerbate genetic predispositions to high adult SBP. However, this effect was observed primarily in individuals with BMI values above 22 kg/m² for females and 19 kg/m² for males, with caution advised for BMI values above 35 kg/m² due to sparse data. These associations showed sex-specific differences, where BMI had a stronger direct effect on SBP in males, while genetic risk scores explained more variance in SBP for females. This study highlights the need for early weight management (in adolescents) to prevent adult SBP-related complications.

Background

High blood pressure (BP) is one of the most prevalent contributors to human preventable mortality. Research has revealed strong associations between high BP and several chronic non-communicable diseases, including kidney and cardiovascular diseases (CVDs). This knowledge has seeded several studies aimed at identifying the causes of high BP and the means to prevent its manifestation.

Recent research suggests a link between BP in adolescents (age ≥ 13) and suboptimal adult BP outcomes, highlighting the need for effective BP management in youth to prevent chronic disease manifestations during adulthood. Separately, genome-wide association studies (GWASs) have identified genetic determinants of adult high BP risk, indicating a heritable (genetic predisposition) component to the condition. Notably, the International Consortium for Blood Pressure (ICBP) (2011) initially identified 29 single-nucleotide polymorphisms (SNPs) associated with elevated BP, which expanded to 564 in 2018.

Unfortunately, scientists remain hitherto unaware of the optimal strategies to mitigate adolescent BP’s association with adult BP. Furthermore, most BP-associated GWAS have focused on adults, with a limited understanding of how these genetic variants influence blood pressure in younger populations.

About the Study

The present study seeks to identify if adolescent BMI can alter the association between genetic predisposition and elevated systolic BP (SBP) risk in adults. Furthermore, it seeks to unravel any underlying sex-specific association between these variables.

Study participants were obtained from the Nicotine Dependence in Teens (NDIT) study, a longitudinal study spanning 18 years that originally recruited 1,294 students (12-13 years) in 1999-2000 from secondary schools in the Montreal area. All participants were of European descent, which may limit the generalizability of findings to more diverse populations. Data collection included questionnaires administered during adolescence, followed by follow-ups at ages 20, 24, 30, 34, and 36. Additionally, BMI and BP measurements and biological samples (blood at age 14, saliva at ages 20 and 25) were collected.

Blood and saliva samples were used to generate participant-specific genotyping data for 636,454 SNPs using the Illumina Infinium HD Global platform. Simultaneously, previous adult GWAS datasets were used to create two genetic risk scores (GRS22 and GRS182), comprising SNPs with known genetic associations with adult SBP.

Statistical modeling involved using linear mixed models to elucidate sex-specific associations between participant SNP data, GRS (22 or 182), and adult SBP outcomes. To better understand the effects of BMI on adult SBP outcomes, a GRS*BMI interaction term was created, allowing researchers to test whether BMI altered genetic risk. Additionally, a leave-one-out method was applied to eliminate noninformative SNPs from the GRS182 dataset, enhancing its predictive accuracy.

Study Findings

Of the 1,294 participants screened from the NDIT study, 714 (53.8% female) met present study requirements and were included in analyses. Baseline SBP values demonstrated a mean of 104.7 mm Hg in 12-year-old females and 106.1 mm Hg in males, increasing to 103.9 mm Hg and 114.5 mm Hg, respectively, at age 30. Notably, both female and male BMIs increased from ages 12-30 (20.2-25.5 kg/m² in females and 20.2-26.1 kg/m² in males).

Analysis results revealed that both age and sex significantly predicted SBP levels. Age is an expected predictor (older individuals are more likely to have higher SBP), while the study also found a sex-based difference in genetic risk, where genetic risk scores explained more SBP variance in females, while BMI had a stronger influence on SBP in males. Furthermore, no SNPs were found to be directly associated with both BMI and SBP, suggesting that BMI and genetic factors may act independently.

GRS182 proved to be a more accurate predictor of adult SBP risk than GRS22, particularly in females, explaining up to 5.6% of SBP variance compared to

Study Limitations

The study had some limitations, including its relatively small sample size (714 participants), which may have constrained its ability to detect subtle genetic effects. Additionally, all participants were of European ancestry, limiting its applicability to other populations. Future research should examine whether these findings hold true in more diverse ethnic groups.

Clinical Implications

The study suggests that while genetic risk scores (GRS) can predict SBP to some extent, their explanatory power remains modest (up to 5.6% variance in females and less than 1% in males). This indicates that BMI remains a more influential and practical target for intervention in youth. The findings suggest that early lifestyle interventions—such as diet and exercise modifications—may be particularly beneficial for individuals with high BMI to reduce their lifetime risk of hypertension.

Conclusions

The present study reveals that adolescent BMI can significantly exacerbate genetic risk for elevated SBP in adulthood, highlighting the need for early BMI monitoring and weight management in youth. The study also found a sex-specific association, with BMI modifying genetic risk differently in males and females.