Genetic Variants Associated With Systolic Blood Pressure in Children and Adolescents.
Mindy Marie PikeJonathan S SchildcroutH Scott BaldwinTodd L EdwardsLoren LipworthCassianne Robinson-CohenPublished in: Journal of the American Heart Association (2023)
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.
Keyphrases
- blood pressure
- genome wide
- genome wide association study
- dna methylation
- hypertensive patients
- body mass index
- heart rate
- copy number
- heart failure
- physical activity
- left ventricular
- metabolic syndrome
- cardiovascular disease
- early life
- gene expression
- type diabetes
- blood glucose
- young adults
- high density
- insulin resistance
- genetic diversity
- childhood cancer
- genome wide association
- neural network