Body mass index modifies genetic susceptibility to high systolic blood pressure in adolescents and young adults: results from an 18-year longitudinal study.

Genome-wide association studies (GWAS) in adults have identified single nucleotide polymorphisms (SNPs) associated with systolic blood pressure (SBP), but it is unclear whether the findings apply in youth. Further, the role of body mass index (BMI) in these associations is understudied. Our objective was to determine whether BMI modifies genetic susceptibility to high SBP in young people. The sample comprised 714 participants of European ancestry recruited in 1999-2000 from 10 Montreal-area high schools for a longitudinal study. SBP was measured at ages 12, 15, 17, 24, and 30. Blood and saliva samples were collected at ages 14, 20, and 25. Two evidence-based genetic risk scores (GRS) were constructed based on GWAS results in adults: GRS₂₂ used 22 SNPs and GRS₁₈₂ added 160 additional SNPs to GRS₂₂. Sex-specific associations between each GRS and repeated measures of SBP were estimated using linear mixed models including BMI and a GRS*BMI product term. GRS₁₈₂ explained a greater proportion of SBP variance than GRS₂₂, and a greater proportion in females than males. The associations increased monotonically with BMI values between 22 kg/m² and 35 kg/m². Results indicate that BMI modifies the association between a GRS and SBP levels from adolescence to adulthood.