Author:
Gouveia Mateus H.,Bentley Amy R.,Leonard Hampton,Meeks Karlijn A. C.,Ekoru Kenneth,Chen Guanjie,Nalls Michael A.,Simonsick Eleanor M.,Tarazona-Santos Eduardo,Lima-Costa Maria Fernanda,Adeyemo Adebowale,Shriner Daniel,Rotimi Charles N.
Abstract
AbstractGenome-wide association studies (GWAS) have identified thousands of genetic loci associated with cross-sectional blood pressure (BP) traits; however, GWAS based on longitudinal BP have been underexplored. We performed ethnic-specific and trans-ethnic GWAS meta-analysis using longitudinal and cross-sectional BP data of 33,720 individuals from five cohorts in the US and one in Brazil. In addition to identifying several known loci, we identified thirteen novel loci with nine based on longitudinal and four on cross-sectional BP traits. Most of the novel loci were ethnic- or study-specific, with the majority identified in African Americans (AA). Four of these discoveries showed additional evidence of association in independent datasets, including an intergenic variant (rs4060030, p = 7.3 × 10–9) with reported regulatory function. We observed a high correlation between the meta-analysis results for baseline and longitudinal average BP (rho = 0.48). BP trajectory results were more correlated with those of average BP (rho = 0.35) than baseline BP(rho = 0.18). Heritability estimates trended higher for longitudinal traits than for cross-sectional traits, providing evidence for different genetic architectures. Furthermore, the longitudinal data identified up to 20% more BP known associations than did cross-sectional data. Our analyses of longitudinal BP data in diverse ethnic groups identified novel BP loci associated with BP trajectory, indicating a need for further longitudinal GWAS on BP and other age-related traits.
Funder
National Human Genome Research Institute
National Institute on Aging
Pró-Reitoria de Pesquisa, Universidade Federal de Minas Gerais
Fundação Oswaldo Cruz
National Institutes of Health
Publisher
Springer Science and Business Media LLC
Cited by
10 articles.
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