TY - JOUR
T1 - Trans-ethnic meta-analysis identifies new loci associated with longitudinal blood pressure traits
AU - Gouveia, Mateus H.
AU - Bentley, Amy R.
AU - Leonard, Hampton
AU - Meeks, Karlijn A.C.
AU - Ekoru, Kenneth
AU - Chen, Guanjie
AU - Nalls, Michael A.
AU - Simonsick, Eleanor M.
AU - Tarazona-Santos, Eduardo
AU - Lima-Costa, Maria Fernanda
AU - Adeyemo, Adebowale
AU - Shriner, Daniel
AU - Rotimi, Charles N.
N1 - Funding Information:
Open Access funding provided by the National Institutes of Health (NIH). This project is supported by the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health (NIH) through the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is also supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the Office of the Director at the NIH (Z01HG200362). The EPIGEN-Brazil Initiative is funded by the Brazilian Ministry of Health (Department of Science and Technology from the Secretaria de Ciência, Tecnologia e Insumos Estratégicos) through Financiadora de Estudos e Projetos. The EPIGEN-Brazil investigators received funding from the Brazilian Ministry of Education (CAPES Agency). MFLC and ETS were supported by Brazilian National Research Council (CNPq), Minas Gerais Research Agency (FAPEMIG) and Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Genome-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.
AB - Genome-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.
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U2 - 10.1038/s41598-021-83450-3
DO - 10.1038/s41598-021-83450-3
M3 - Article
C2 - 33603002
AN - SCOPUS:85101265711
SN - 2045-2322
VL - 11
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 4075
ER -