A higher BMI in adolescence worsens the genetic risk of high blood pressure, the study studies

A higher BMI in adolescence worsens the genetic risk of high blood pressure, the study studies

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

In a recently published study in theJournal of Human HypertensionResearchers used a large, long-term data set to elucidate whether youth body mass index (BMI) can alter young people's genetic predisposition to systolic blood pressure (SBP). Their dataset included 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).

At the same time, researchers created two genetic risk scores (GRs) derived from genome-wide association studies (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with adult SBP. GRS182, which included more SNPs than GRS22, became a stronger predictor of SBP in adulthood, explaining up to 5.6% of SBP variance in women but less than 1% in men.

Linear mixed models showed that increased BMI values ​​(22 kg/m² to 35 kg/m²) progressively amplified the associations between GRS and SBP, confirming that higher adolescent BMIs may exacerbate genetic predispositions to high adult SBP. However, this effect was mainly observed in individuals with BMI values ​​above 22 kg/m² for women and 19 kg/m² for men, with caution recommended for BMI values ​​above 35 kg/m² based on savings data. These associations revealed gender differences, where BMI had a stronger direct influence on SBP for men, while genetic risk scores explained more variance in SBP for women. This study demonstrates the need for early weight management (in adolescents) to prevent the adult complications associated with SBP.

background

The study found that systolic blood pressure (SBP) increased steadily from adolescence to adulthood in men, while it remained more stable over time in women, suggesting sex-based physiological differences in blood pressure regulation.

Hypertension (BP) is one of the most commonly targeted contributors to preventable human mortality. Research has found strong associations between high blood pressure and several chronic non-communicable diseases, including kidney and cardiovascular diseases (CVDs). This knowledge has seeded several studies to identify the causes of high blood pressure and the means to prevent its manifestation.

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

Unfortunately, scientists remain unaware of the optimal strategies for reducing adolescents' association with adult blood pressure. Furthermore, most BP-associated GWAs have focused on adults, with limited understanding of how these genetic variants influence BP in younger populations.

About the study

The present study aims to determine whether adolescent BMI can modify the association between genetic predisposition and increased systolic BP (SBP) risk in adults. Furthermore, it attempts to unravel any underlying gender associations between these variables.

Study participants were obtained from the Nicotine Dependence in Teens Studies (NDIT), an 18-year longitudinal study that initially recruited 1,294 students (12-13 years old) from secondary schools in the Montreal region in 1999-2000. All participants were of European descent, which may limit the generalizability of results 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. At the same time, previous adult GWAS datasets were used to create two genetic risk scores (GRS22 and GRS182) that include SNPs with known genetic associations with adult SBP.

Statistical modeling included the use of linear mixed models to elucidate sex-specific associations between participant SNP data, GRS (22 or 182), and adult SBP outcomes. To better understand the impact of BMI on adult SBP outcomes, a BMI interaction term was created by GRS* so researchers could test whether BMI modified genetic risk. In addition, a leave-one-out method was applied to eliminate uninformative SNPs from the GRS182 dataset, thereby improving the prediction accuracy.

Study results

While BMI and genetic risk both contributed to higher SBP, no direct link was found between BMI and individual genetic variants, suggesting that these factors influence blood pressure through separate biological pathways.

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

Analysis results showed that both age and gender 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, with genetic risk scores explaining more SBP variance in women, while BMI had a stronger influence on SBP in men. Furthermore, no SNPs were found to be directly associated with BMI and SBP, suggesting that BMI and genetic factors may act independently.

GRS182 was found to be a more accurate predictor of adult SBP risk than GRS22, particularly in women, explaining up to 5.6% of SBP variance compared to <1% in men. Notably, both GRS values ​​were strongly influenced by BMI, but the modifying effect of BMI was only observed at higher BMI values ​​(above 22 kg/m² for women and 19 kg/m² for men).

Study limitations

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

Clinical implications

The study suggests that although genetic risk scores (GRS) can predict SBP to some extent, their explanatory power remains modest (up to 5.6% variance in women and less than 1% in men). This suggests 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 modification – are particularly beneficial for people with high BMI to reduce their lifetime risk of high blood pressure.

Conclusions

The present study shows that adolescent BMI may significantly exacerbate the genetic risk for elevated SBP in adulthood, highlighting the need for early BMI monitoring and weight management in adolescents. The study also found a gender association, with BMI modifying genetic risk differently in men and women.

Sources: