Abstract
BACKGROUND: The objective of this study was to investigate the genetic association of 4 candidate variants with blood pressure and test the modifying effects of environmental factors including age, sex, and body mass index (BMI). METHODS: We used a linear mixed-effects model to test for variant main effects and variant interactions with age, sex, and BMI on systolic (SBP) and diastolic (DBP) blood pressure in 7,319 Chinese adults from the China Health and Nutrition Survey (CHNS). We attempted to replicate our significant interaction findings in 1,996 Chinese men from the Fangchenggang Area Male Health and Examination Survey (FAMHES). RESULTS: Two variants (rs11105378 near ATP2B1 and rs1458038 near FGF5) were significantly associated (P < 0.00625 = 0.05/8) with both SBP and DBP in CHNS. Variant rs1378942 near CSK was nominally associated with SBP (P = 0.01). The signal at rs1458038 exhibited a genotype-by-BMI interaction affecting blood pressure (P interaction = 0.0018 for SBP; P interaction = 0.049 for DBP), with the strongest variant effects in those with the highest BMI. In FAMHES, rs1458038 also showed stronger effects on SBP and DBP among men with the highest BMI. CONCLUSIONS: Our findings suggest high BMI increases the effect of the blood pressure-increasing allele at rs1458038 near FGF5, further highlighting the importance of obesity prevention in reducing hypertension risk.