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Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study

BACKGROUND: Local ancestry in relation to clinical cardiovascular events (CVEs) among African Americans can provide insight into their genetic susceptibility to the disease. METHODS AND RESULTS: We examined local European ancestry (LEA) association with CVEs among 3000 African Americans from the Ath...

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Autores principales: Shendre, Aditi, Irvin, Marguerite R., Wiener, Howard, Zhi, Degui, Limdi, Nita A., Overton, Edgar T., Shrestha, Sadeep
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532995/
https://www.ncbi.nlm.nih.gov/pubmed/28396569
http://dx.doi.org/10.1161/JAHA.116.004739
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author Shendre, Aditi
Irvin, Marguerite R.
Wiener, Howard
Zhi, Degui
Limdi, Nita A.
Overton, Edgar T.
Shrestha, Sadeep
author_facet Shendre, Aditi
Irvin, Marguerite R.
Wiener, Howard
Zhi, Degui
Limdi, Nita A.
Overton, Edgar T.
Shrestha, Sadeep
author_sort Shendre, Aditi
collection PubMed
description BACKGROUND: Local ancestry in relation to clinical cardiovascular events (CVEs) among African Americans can provide insight into their genetic susceptibility to the disease. METHODS AND RESULTS: We examined local European ancestry (LEA) association with CVEs among 3000 African Americans from the Atherosclerosis Risk in Communities Study (ARIC). We estimated LEA using Local Ancestry Inference in adMixed Populations using Linkage Disequilibrium (LAMP‐LD) and examined its association with myocardial infarction, stroke, coronary heart disease and its composite and cardiovascular disease composite using logistic regression. Genome‐wide significance was achieved by 121 LEA regions in relation to myocardial infarction and 2 in relation to the cardiovascular disease composite. The LEA region downstream of 4q32.1 was significantly associated with 2 times higher odds of myocardial infarction (P=1.45×10(−6)). The LEA region upstream of 6q11.1 was associated with 0.37 times lower odds of fatal coronary heart disease (P=7.34×10(−4)), whereas the LEA region downstream of 21q21.1 was associated with 1.55 times higher odds of composite coronary heart disease (P=3.45×10(−4)). Association of LEA with stroke was observed in the region upstream of 6p22.3 with a 1.57 times higher odds of stroke (P=9.69×10(−4)). Likewise, the LEA region on 4q32.3 was associated with a 1.53 times higher odds of composite cardiovascular disease (P=3.04×10(−4)). We also found 20 of the LEA regions at previously significant cardiovascular disease single‐nucleotide polymorphisms to be associated with CVE in our study. CONCLUSIONS: Future studies are needed to replicate and/or determine the causal variants driving our associations and explore clinical applications for those consistently associated with CVEs.
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spelling pubmed-55329952017-08-14 Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study Shendre, Aditi Irvin, Marguerite R. Wiener, Howard Zhi, Degui Limdi, Nita A. Overton, Edgar T. Shrestha, Sadeep J Am Heart Assoc Original Research BACKGROUND: Local ancestry in relation to clinical cardiovascular events (CVEs) among African Americans can provide insight into their genetic susceptibility to the disease. METHODS AND RESULTS: We examined local European ancestry (LEA) association with CVEs among 3000 African Americans from the Atherosclerosis Risk in Communities Study (ARIC). We estimated LEA using Local Ancestry Inference in adMixed Populations using Linkage Disequilibrium (LAMP‐LD) and examined its association with myocardial infarction, stroke, coronary heart disease and its composite and cardiovascular disease composite using logistic regression. Genome‐wide significance was achieved by 121 LEA regions in relation to myocardial infarction and 2 in relation to the cardiovascular disease composite. The LEA region downstream of 4q32.1 was significantly associated with 2 times higher odds of myocardial infarction (P=1.45×10(−6)). The LEA region upstream of 6q11.1 was associated with 0.37 times lower odds of fatal coronary heart disease (P=7.34×10(−4)), whereas the LEA region downstream of 21q21.1 was associated with 1.55 times higher odds of composite coronary heart disease (P=3.45×10(−4)). Association of LEA with stroke was observed in the region upstream of 6p22.3 with a 1.57 times higher odds of stroke (P=9.69×10(−4)). Likewise, the LEA region on 4q32.3 was associated with a 1.53 times higher odds of composite cardiovascular disease (P=3.04×10(−4)). We also found 20 of the LEA regions at previously significant cardiovascular disease single‐nucleotide polymorphisms to be associated with CVE in our study. CONCLUSIONS: Future studies are needed to replicate and/or determine the causal variants driving our associations and explore clinical applications for those consistently associated with CVEs. John Wiley and Sons Inc. 2017-04-10 /pmc/articles/PMC5532995/ /pubmed/28396569 http://dx.doi.org/10.1161/JAHA.116.004739 Text en © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Shendre, Aditi
Irvin, Marguerite R.
Wiener, Howard
Zhi, Degui
Limdi, Nita A.
Overton, Edgar T.
Shrestha, Sadeep
Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study
title Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study
title_full Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study
title_fullStr Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study
title_full_unstemmed Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study
title_short Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study
title_sort local ancestry and clinical cardiovascular events among african americans from the atherosclerosis risk in communities study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532995/
https://www.ncbi.nlm.nih.gov/pubmed/28396569
http://dx.doi.org/10.1161/JAHA.116.004739
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