adrenergic alpha-1 pathway is associated with hypertension among nigerians in a pathway-focused analysis肾上腺素的alpha -通路与高血压有关在尼日利亚pathway-focused分析.pdfVIP
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adrenergic alpha-1 pathway is associated with hypertension among nigerians in a pathway-focused analysis肾上腺素的alpha -通路与高血压有关在尼日利亚pathway-focused分析
Adrenergic Alpha-1 Pathway Is Associated with
Hypertension among Nigerians in a Pathway-focused
Analysis
1 1 2 2 3
Nicholas P. Reder *, Bamidele O. Tayo , Babatunde Salako , Adesola Ogunniyi , Adebowale Adeyemo ,
Charles Rotimi3, Richard S. Cooper1
1 Department of Preventive Medicine and Epidemiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, United States of America, 2 Department
of Medicine, University of Ibadan, Ibadan, Nigeria, 3 National Institutes of Health Intramural Center for Research on Genomics and Global Health, National Human Genome
Research Institute, Bethesda, Maryland, United States of America
Abstract
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 Pgene,0.004, DBP Pgene,0.004, and SBP Pgene ,0.009, and ADRA1B
(hypertension Pgene,0.005, DBP Pgene ,0.02, and SBP Pgene,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 AD
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