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A genome‐wide association and replication study of blood pressure in Ugandan early adolescents

BACKGROUND: Genetic association studies of blood pressure (BP) have mostly been conducted in non‐African populations. Using the Entebbe Mother and Baby Study (EMaBS), we aimed to identify genetic variants associated with BP among Ugandan adolescents. METHODS: Systolic and diastolic BP were measured...

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Autores principales: Lule, Swaib A., Mentzer, Alexander J., Namara, Benigna, Muwenzi, Allan G., Nassanga, Beatrice, kizito, Dennison, Akurut, Helen, Lubyayi, Lawrence, Tumusiime, Josephine, Zziwa, Christopher, Akello, Florence, Gurdasani, Deept, Sandhu, Manjinder, Smeeth, Liam, Elliott, Alison M., Webb, Emily L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785527/
https://www.ncbi.nlm.nih.gov/pubmed/31469255
http://dx.doi.org/10.1002/mgg3.950
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author Lule, Swaib A.
Mentzer, Alexander J.
Namara, Benigna
Muwenzi, Allan G.
Nassanga, Beatrice
kizito, Dennison
Akurut, Helen
Lubyayi, Lawrence
Tumusiime, Josephine
Zziwa, Christopher
Akello, Florence
Gurdasani, Deept
Sandhu, Manjinder
Smeeth, Liam
Elliott, Alison M.
Webb, Emily L.
author_facet Lule, Swaib A.
Mentzer, Alexander J.
Namara, Benigna
Muwenzi, Allan G.
Nassanga, Beatrice
kizito, Dennison
Akurut, Helen
Lubyayi, Lawrence
Tumusiime, Josephine
Zziwa, Christopher
Akello, Florence
Gurdasani, Deept
Sandhu, Manjinder
Smeeth, Liam
Elliott, Alison M.
Webb, Emily L.
author_sort Lule, Swaib A.
collection PubMed
description BACKGROUND: Genetic association studies of blood pressure (BP) have mostly been conducted in non‐African populations. Using the Entebbe Mother and Baby Study (EMaBS), we aimed to identify genetic variants associated with BP among Ugandan adolescents. METHODS: Systolic and diastolic BP were measured among 10‐ and 11‐year olds. Whole‐genome genotype data were generated using Illumina omni 2.5M arrays and untyped variants were imputed. Genome‐wide association study (GWAS) was conducted using linear mixed model regression to account for population structure. Linear regression analysis was used to assess whether variants previously associated with BP (p < 5.0 × 10(−8)) in published BP GWASs were replicated in our study. RESULTS: Of the 14 million variants analyzed among 815 adolescents, none reached genome‐wide significance (p < 5.0×10(−8)) for association with systolic or diastolic BP. The most strongly associated variants were rs181430167 (p = 6.8 × 10(−7)) for systolic BP and rs12991132 (p = 4.0 × 10(−7)) for diastolic BP. Thirty‐three (17 single nucleotide polymorphisms (SNPs) for systolic BP, 15 SNPs for diastolic BP and one SNP for both) of 330 variants previously identified as associated with BP were replicated in this study, but none remained significant after accounting for multiple testing. CONCLUSION: Variants showing suggestive associations are worthy of future investigation. Replication results suggest that variants influencing adolescent BP may overlap somewhat with those already established in previous studies, largely based on adults in Western settings.
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spelling pubmed-67855272019-10-17 A genome‐wide association and replication study of blood pressure in Ugandan early adolescents Lule, Swaib A. Mentzer, Alexander J. Namara, Benigna Muwenzi, Allan G. Nassanga, Beatrice kizito, Dennison Akurut, Helen Lubyayi, Lawrence Tumusiime, Josephine Zziwa, Christopher Akello, Florence Gurdasani, Deept Sandhu, Manjinder Smeeth, Liam Elliott, Alison M. Webb, Emily L. Mol Genet Genomic Med Original Articles BACKGROUND: Genetic association studies of blood pressure (BP) have mostly been conducted in non‐African populations. Using the Entebbe Mother and Baby Study (EMaBS), we aimed to identify genetic variants associated with BP among Ugandan adolescents. METHODS: Systolic and diastolic BP were measured among 10‐ and 11‐year olds. Whole‐genome genotype data were generated using Illumina omni 2.5M arrays and untyped variants were imputed. Genome‐wide association study (GWAS) was conducted using linear mixed model regression to account for population structure. Linear regression analysis was used to assess whether variants previously associated with BP (p < 5.0 × 10(−8)) in published BP GWASs were replicated in our study. RESULTS: Of the 14 million variants analyzed among 815 adolescents, none reached genome‐wide significance (p < 5.0×10(−8)) for association with systolic or diastolic BP. The most strongly associated variants were rs181430167 (p = 6.8 × 10(−7)) for systolic BP and rs12991132 (p = 4.0 × 10(−7)) for diastolic BP. Thirty‐three (17 single nucleotide polymorphisms (SNPs) for systolic BP, 15 SNPs for diastolic BP and one SNP for both) of 330 variants previously identified as associated with BP were replicated in this study, but none remained significant after accounting for multiple testing. CONCLUSION: Variants showing suggestive associations are worthy of future investigation. Replication results suggest that variants influencing adolescent BP may overlap somewhat with those already established in previous studies, largely based on adults in Western settings. John Wiley and Sons Inc. 2019-08-30 /pmc/articles/PMC6785527/ /pubmed/31469255 http://dx.doi.org/10.1002/mgg3.950 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Lule, Swaib A.
Mentzer, Alexander J.
Namara, Benigna
Muwenzi, Allan G.
Nassanga, Beatrice
kizito, Dennison
Akurut, Helen
Lubyayi, Lawrence
Tumusiime, Josephine
Zziwa, Christopher
Akello, Florence
Gurdasani, Deept
Sandhu, Manjinder
Smeeth, Liam
Elliott, Alison M.
Webb, Emily L.
A genome‐wide association and replication study of blood pressure in Ugandan early adolescents
title A genome‐wide association and replication study of blood pressure in Ugandan early adolescents
title_full A genome‐wide association and replication study of blood pressure in Ugandan early adolescents
title_fullStr A genome‐wide association and replication study of blood pressure in Ugandan early adolescents
title_full_unstemmed A genome‐wide association and replication study of blood pressure in Ugandan early adolescents
title_short A genome‐wide association and replication study of blood pressure in Ugandan early adolescents
title_sort genome‐wide association and replication study of blood pressure in ugandan early adolescents
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785527/
https://www.ncbi.nlm.nih.gov/pubmed/31469255
http://dx.doi.org/10.1002/mgg3.950
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