Hypertension affects nearly one-third of adults over age 20 in the United States. While hypertension is found in <10% in adults 20 - 34 years of age, it develops over a period of years, and blood pressure levels in children and adolescents are correlated with levels in adults. It is clear that genes play a significant role in regulating blood pressure, but little is known about the effects of genetic variation on the blood pressure changes that occur with age. Identifying the genes and mutations that affect blood pressure change from childhood, through adolescence, and into adulthood is necessary if are to understand the pathology of hypertension and target preventive measures most effectively. The Bogalusa Heart Study (BHS), which began as a study of cardiovascular disease (CVD) risk factors in children but evolved to cover the development of CVD risk factors from childhood into adulthood, offers a matchless resource for investigating the genetic factors influencing within-individual changes over time from childhood to adulthood in blood pressure and other CVD risk factors. We propose to investigate 3072 single-nucleotide polymorphisms (SNPs), both individually and as multilocus haplotypes (combinations of SNP alleles on a single chromosome), in 115 genes known or strongly suspected to affect blood pressure and risk of hypertension, using 1735 BHS subjects who consented to participate in studies of the genetics of CVD risk factors. Of these, 1687 (97.2%) were examined at least twice. The sample includes 1195 whites (with 5927 examinations) and 540 African Americans (with 2677 examinations);subjects were from 3 - 38 years of age when examined. Multilevel regression will be used to measure the effect of individual SNPs on longitudinal blood pressure profiles and identify those that affect age-related changes in blood pressure. In genes in which individual SNPs show significant associations, follow-up multilocus analyses will use evolutionary relationships among haplotypes to determine appropriate sets of haplotype comparisons to identify specific haplotypes associated with blood pressure changes over time and aid in locating functional mutations while reducing the number of necessary tests and increasing statistical power. All SNPs and haplotypes showing positive associations in the BHS cohort will be genotyped and analyzed in a replication sample of 506 whites (with 4503 examinations) and 136 African Americans (with 1007 examinations) drawn from Project HeartBeat!, a study of CVD risk factors in which schoolchildren from two Texas communities were enrolled at 8, 11, or 14 years of age, then received medical examinations 3 times a year for 4 years. The proposed research, involving the only two cohorts for whom extensive longitudinal data exist for biracial populations that include substantial numbers of African Americans, will greatly extend our knowledge of the genetic factors that affect blood pressure over a large portion of the human lifespan. Because many genes that affect blood pressure may also affect traits such as obesity and serum lipid levels, the proposed research will also provide opportunities to investigate genes affecting changes in other CVD risk factors.
Hypertension affects nearly one-third of adults in the United States, and though frank hypertension is uncommon in adults under 34 years of age, blood pressure levels in children and adolescents are correlated with levels in adults. It is clear that genes play a significant role in regulating blood pressure, but little is known about the effects of genes on the blood pressure changes that occur with age. Our proposed study will investigate genes likely to affect blood pressure changes over time in individuals 3-38 years of age, and will greatly extend our knowledge of the genetic factors that affect blood pressure over a large portion of the human lifespan.
| Hallman, D M; Friedel, V C; Eissa, M A H et al. (2012) The association of variants in the FTO gene with longitudinal body mass index profiles in non-Hispanic white children and adolescents. Int J Obes (Lond) 36:61-8 |
