Genetic Variants Associated With Systolic Blood Pressure in Children and Adolescents

Abstract

Background Genetics, along with lifestyle and behavioral characteristics, play an important role in hypertension in adults. Our aim was to identify genetic variants associated with blood pressure in childhood and adolescence. Methods and Results We conducted a candidate single-nucleotide polymorphism (SNP) analysis and genome-wide association study among 9778 participants aged <18 years in BioVU, the Vanderbilt University Medical Center biobank. The outcome was childhood blood pressure percentile from age 0 to 18 years. For the candidate SNP analysis, a total of 457 previously identified SNPs were examined. Linear regression was used to test the association between genetic variants and median systolic blood pressure (SBP) percentile. Adjusted models included median age, self-reported sex, race, the first 4 principal components of ancestry, and median body mass index Z score. Analyses were conducted in the overall cohort and stratified by age group. A polygenic risk score was calculated for each participant, and the association between polygenic risk score and median SBP percentile in childhood was examined using linear regression. In the overall candidate SNP analysis, 2 SNPs reached significance: rs1018148 (FBN1; P=1.0×10^-4) and rs11105354 (ATP2B1; P=1.4×10^-4). In the postpuberty age group, 1 SNP reached significance: rs1018148 (FBN1; P=2.2×10^-5). In the genome-wide association study of all participants, no SNPs reached genome-wide significance. Higher polygenic risk score was associated with higher SBP percentile (β, 0.35 [95% CI, 0.10-0.60)], and there was a significant interaction with age (P for interaction<0.01). Conclusions These findings suggest that genetic variants play an important role in SBP in childhood and adolescence and provide evidence for age-specific genetic associations with SBP.

Keywords: childhood; genome‐wide association study; single‐nucleotide polymorphism; systolic blood pressure.

Figure 1. Manhattan plot for the genome‐wide association study of all participants (N=9778).

Figure 2. Quantile‐quantile plot for the genome‐wide association study of all participants (N=9778).

Figure 3. Manhattan plots for age‐stratified genome‐wide association study: 0 to 3 years (A), 4 to 7 years (B), 8 to 12 years (C), and 13 to 18 years (D).

Figure 4. Quantile‐quantile plots for the age‐stratified genome‐wide association study: 0 to 3 years (A), 4 to 7 years (B), 8 to 12 years (C), and 13 to 18 years (D).