Cargando…

Trans-ethnic meta-analysis identifies new loci associated with longitudinal blood pressure traits

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-s...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893038/
https://www.ncbi.nlm.nih.gov/pubmed/33603002
http://dx.doi.org/10.1038/s41598-021-83450-3
_version_ 1783652980500725760
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.
author_facet 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.
author_sort Gouveia, Mateus H.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7893038
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-78930382021-02-23 Trans-ethnic meta-analysis identifies new loci associated with longitudinal blood pressure traits 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. Sci Rep Article 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. Nature Publishing Group UK 2021-02-18 /pmc/articles/PMC7893038/ /pubmed/33603002 http://dx.doi.org/10.1038/s41598-021-83450-3 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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.
Trans-ethnic meta-analysis identifies new loci associated with longitudinal blood pressure traits
title Trans-ethnic meta-analysis identifies new loci associated with longitudinal blood pressure traits
title_full Trans-ethnic meta-analysis identifies new loci associated with longitudinal blood pressure traits
title_fullStr Trans-ethnic meta-analysis identifies new loci associated with longitudinal blood pressure traits
title_full_unstemmed Trans-ethnic meta-analysis identifies new loci associated with longitudinal blood pressure traits
title_short Trans-ethnic meta-analysis identifies new loci associated with longitudinal blood pressure traits
title_sort trans-ethnic meta-analysis identifies new loci associated with longitudinal blood pressure traits
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893038/
https://www.ncbi.nlm.nih.gov/pubmed/33603002
http://dx.doi.org/10.1038/s41598-021-83450-3
work_keys_str_mv AT gouveiamateush transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT bentleyamyr transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT leonardhampton transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT meekskarlijnac transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT ekorukenneth transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT chenguanjie transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT nallsmichaela transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT simonsickeleanorm transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT tarazonasantoseduardo transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT limacostamariafernanda transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT adeyemoadebowale transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT shrinerdaniel transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits
AT rotimicharlesn transethnicmetaanalysisidentifiesnewlociassociatedwithlongitudinalbloodpressuretraits