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Adrenergic Alpha-1 Pathway Is Associated with Hypertension among Nigerians in a Pathway-focused Analysis
BACKGROUND: The pathway-focused association approach offers a hypothesis driven alternative to the agnostic genome-wide association study. Here we apply the pathway-focused approach to an association study of hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in 1614 Nig...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353888/ https://www.ncbi.nlm.nih.gov/pubmed/22615923 http://dx.doi.org/10.1371/journal.pone.0037145 |
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author | Reder, Nicholas P. Tayo, Bamidele O. Salako, Babatunde Ogunniyi, Adesola Adeyemo, Adebowale Rotimi, Charles Cooper, Richard S. |
author_facet | Reder, Nicholas P. Tayo, Bamidele O. Salako, Babatunde Ogunniyi, Adesola Adeyemo, Adebowale Rotimi, Charles Cooper, Richard S. |
author_sort | Reder, Nicholas P. |
collection | PubMed |
description | BACKGROUND: The pathway-focused association approach offers a hypothesis driven alternative to the agnostic genome-wide association study. Here we apply the pathway-focused approach to an association study of hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in 1614 Nigerians with genome-wide data. METHODS AND RESULTS: Testing of 28 pathways with biological relevance to hypertension, selected a priori, containing a total of 101 unique genes and 4,349 unique single-nucleotide polymorphisms (SNPs) showed an association for the adrenergic alpha 1 (ADRA1) receptor pathway with hypertension (p<0.0009) and diastolic blood pressure (p<0.0007). Within the ADRA1 pathway, the genes PNMT (hypertension P(gene)<0.004, DBP P(gene)<0.004, and SBP P(gene)<0.009, and ADRA1B (hypertension P(gene)<0.005, DBP P(gene)<0.02, and SBP P(gene)<0.02) displayed the strongest associations. Neither ADRA1B nor PNMT could be the sole mediator of the observed pathway association as the ADRA1 pathway remained significant after removing ADRA1B, and other pathways involving PNMT did not reach pathway significance. CONCLUSIONS: We conclude that multiple variants in several genes in the ADRA1 pathway led to associations with hypertension and DBP. SNPs in ADRA1B and PNMT have not previously been linked to hypertension in a genome-wide association study, but both genes have shown associations with hypertension through linkage or model organism studies. The identification of moderately significant (10(−2)>p>10(−5)) SNPs offers a novel method for detecting the “missing heritability” of hypertension. These findings warrant further studies in similar and other populations to assess the generalizability of our results, and illustrate the potential of the pathway-focused approach to investigate genetic variation in hypertension. |
format | Online Article Text |
id | pubmed-3353888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33538882012-05-21 Adrenergic Alpha-1 Pathway Is Associated with Hypertension among Nigerians in a Pathway-focused Analysis Reder, Nicholas P. Tayo, Bamidele O. Salako, Babatunde Ogunniyi, Adesola Adeyemo, Adebowale Rotimi, Charles Cooper, Richard S. PLoS One Research Article BACKGROUND: The pathway-focused association approach offers a hypothesis driven alternative to the agnostic genome-wide association study. Here we apply the pathway-focused approach to an association study of hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in 1614 Nigerians with genome-wide data. METHODS AND RESULTS: Testing of 28 pathways with biological relevance to hypertension, selected a priori, containing a total of 101 unique genes and 4,349 unique single-nucleotide polymorphisms (SNPs) showed an association for the adrenergic alpha 1 (ADRA1) receptor pathway with hypertension (p<0.0009) and diastolic blood pressure (p<0.0007). Within the ADRA1 pathway, the genes PNMT (hypertension P(gene)<0.004, DBP P(gene)<0.004, and SBP P(gene)<0.009, and ADRA1B (hypertension P(gene)<0.005, DBP P(gene)<0.02, and SBP P(gene)<0.02) displayed the strongest associations. Neither ADRA1B nor PNMT could be the sole mediator of the observed pathway association as the ADRA1 pathway remained significant after removing ADRA1B, and other pathways involving PNMT did not reach pathway significance. CONCLUSIONS: We conclude that multiple variants in several genes in the ADRA1 pathway led to associations with hypertension and DBP. SNPs in ADRA1B and PNMT have not previously been linked to hypertension in a genome-wide association study, but both genes have shown associations with hypertension through linkage or model organism studies. The identification of moderately significant (10(−2)>p>10(−5)) SNPs offers a novel method for detecting the “missing heritability” of hypertension. These findings warrant further studies in similar and other populations to assess the generalizability of our results, and illustrate the potential of the pathway-focused approach to investigate genetic variation in hypertension. Public Library of Science 2012-05-16 /pmc/articles/PMC3353888/ /pubmed/22615923 http://dx.doi.org/10.1371/journal.pone.0037145 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Reder, Nicholas P. Tayo, Bamidele O. Salako, Babatunde Ogunniyi, Adesola Adeyemo, Adebowale Rotimi, Charles Cooper, Richard S. Adrenergic Alpha-1 Pathway Is Associated with Hypertension among Nigerians in a Pathway-focused Analysis |
title | Adrenergic Alpha-1 Pathway Is Associated with Hypertension among Nigerians in a Pathway-focused Analysis |
title_full | Adrenergic Alpha-1 Pathway Is Associated with Hypertension among Nigerians in a Pathway-focused Analysis |
title_fullStr | Adrenergic Alpha-1 Pathway Is Associated with Hypertension among Nigerians in a Pathway-focused Analysis |
title_full_unstemmed | Adrenergic Alpha-1 Pathway Is Associated with Hypertension among Nigerians in a Pathway-focused Analysis |
title_short | Adrenergic Alpha-1 Pathway Is Associated with Hypertension among Nigerians in a Pathway-focused Analysis |
title_sort | adrenergic alpha-1 pathway is associated with hypertension among nigerians in a pathway-focused analysis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353888/ https://www.ncbi.nlm.nih.gov/pubmed/22615923 http://dx.doi.org/10.1371/journal.pone.0037145 |
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