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Genetic Variants That Confer Resistance to Malaria Are Associated with Red Blood Cell Traits in African-Americans: An Electronic Medical Record-based Genome-Wide Association Study
To identify novel genetic loci influencing interindividual variation in red blood cell (RBC) traits in African-Americans, we conducted a genome-wide association study (GWAS) in 2315 individuals, divided into discovery (n = 1904) and replication (n = 411) cohorts. The traits included hemoglobin conce...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Genetics Society of America
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704235/ https://www.ncbi.nlm.nih.gov/pubmed/23696099 http://dx.doi.org/10.1534/g3.113.006452 |
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author | Ding, Keyue de Andrade, Mariza Manolio, Teri A. Crawford, Dana C. Rasmussen-Torvik, Laura J. Ritchie, Marylyn D. Denny, Joshua C. Masys, Daniel R. Jouni, Hayan Pachecho, Jennifer A. Kho, Abel N. Roden, Dan M. Chisholm, Rex Kullo, Iftikhar J. |
author_facet | Ding, Keyue de Andrade, Mariza Manolio, Teri A. Crawford, Dana C. Rasmussen-Torvik, Laura J. Ritchie, Marylyn D. Denny, Joshua C. Masys, Daniel R. Jouni, Hayan Pachecho, Jennifer A. Kho, Abel N. Roden, Dan M. Chisholm, Rex Kullo, Iftikhar J. |
author_sort | Ding, Keyue |
collection | PubMed |
description | To identify novel genetic loci influencing interindividual variation in red blood cell (RBC) traits in African-Americans, we conducted a genome-wide association study (GWAS) in 2315 individuals, divided into discovery (n = 1904) and replication (n = 411) cohorts. The traits included hemoglobin concentration (HGB), hematocrit (HCT), RBC count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Patients were participants in the electronic MEdical Records and GEnomics (eMERGE) network and underwent genotyping of ~1.2 million single-nucleotide polymorphisms on the Illumina Human1M-Duo array. Association analyses were performed adjusting for age, sex, site, and population stratification. Three loci previously associated with resistance to malaria—HBB (11p15.4), HBA1/HBA2 (16p13.3), and G6PD (Xq28)—were associated (P ≤ 1 × 10(−6)) with RBC traits in the discovery cohort. The loci replicated in the replication cohort (P ≤ 0.02), and were significant at a genome-wide significance level (P < 5 × 10(−8)) in the combined cohort. The proportions of variance in RBC traits explained by significant variants at these loci were as follows: rs7120391 (near HBB) 1.3% of MCHC, rs9924561 (near HBA1/A2) 5.5% of MCV, 6.9% of MCH and 2.9% of MCHC, and rs1050828 (in G6PD) 2.4% of RBC count, 2.9% of MCV, and 1.4% of MCH, respectively. We were not able to replicate loci identified by a previous GWAS of RBC traits in a European ancestry cohort of similar sample size, suggesting that the genetic architecture of RBC traits differs by race. In conclusion, genetic variants that confer resistance to malaria are associated with RBC traits in African-Americans. |
format | Online Article Text |
id | pubmed-3704235 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
spelling | pubmed-37042352013-07-09 Genetic Variants That Confer Resistance to Malaria Are Associated with Red Blood Cell Traits in African-Americans: An Electronic Medical Record-based Genome-Wide Association Study Ding, Keyue de Andrade, Mariza Manolio, Teri A. Crawford, Dana C. Rasmussen-Torvik, Laura J. Ritchie, Marylyn D. Denny, Joshua C. Masys, Daniel R. Jouni, Hayan Pachecho, Jennifer A. Kho, Abel N. Roden, Dan M. Chisholm, Rex Kullo, Iftikhar J. G3 (Bethesda) Investigations To identify novel genetic loci influencing interindividual variation in red blood cell (RBC) traits in African-Americans, we conducted a genome-wide association study (GWAS) in 2315 individuals, divided into discovery (n = 1904) and replication (n = 411) cohorts. The traits included hemoglobin concentration (HGB), hematocrit (HCT), RBC count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Patients were participants in the electronic MEdical Records and GEnomics (eMERGE) network and underwent genotyping of ~1.2 million single-nucleotide polymorphisms on the Illumina Human1M-Duo array. Association analyses were performed adjusting for age, sex, site, and population stratification. Three loci previously associated with resistance to malaria—HBB (11p15.4), HBA1/HBA2 (16p13.3), and G6PD (Xq28)—were associated (P ≤ 1 × 10(−6)) with RBC traits in the discovery cohort. The loci replicated in the replication cohort (P ≤ 0.02), and were significant at a genome-wide significance level (P < 5 × 10(−8)) in the combined cohort. The proportions of variance in RBC traits explained by significant variants at these loci were as follows: rs7120391 (near HBB) 1.3% of MCHC, rs9924561 (near HBA1/A2) 5.5% of MCV, 6.9% of MCH and 2.9% of MCHC, and rs1050828 (in G6PD) 2.4% of RBC count, 2.9% of MCV, and 1.4% of MCH, respectively. We were not able to replicate loci identified by a previous GWAS of RBC traits in a European ancestry cohort of similar sample size, suggesting that the genetic architecture of RBC traits differs by race. In conclusion, genetic variants that confer resistance to malaria are associated with RBC traits in African-Americans. Genetics Society of America 2013-07-01 /pmc/articles/PMC3704235/ /pubmed/23696099 http://dx.doi.org/10.1534/g3.113.006452 Text en Copyright © 2013 Ding et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigations Ding, Keyue de Andrade, Mariza Manolio, Teri A. Crawford, Dana C. Rasmussen-Torvik, Laura J. Ritchie, Marylyn D. Denny, Joshua C. Masys, Daniel R. Jouni, Hayan Pachecho, Jennifer A. Kho, Abel N. Roden, Dan M. Chisholm, Rex Kullo, Iftikhar J. Genetic Variants That Confer Resistance to Malaria Are Associated with Red Blood Cell Traits in African-Americans: An Electronic Medical Record-based Genome-Wide Association Study |
title | Genetic Variants That Confer Resistance to Malaria Are Associated with Red Blood Cell Traits in African-Americans: An Electronic Medical Record-based Genome-Wide Association Study |
title_full | Genetic Variants That Confer Resistance to Malaria Are Associated with Red Blood Cell Traits in African-Americans: An Electronic Medical Record-based Genome-Wide Association Study |
title_fullStr | Genetic Variants That Confer Resistance to Malaria Are Associated with Red Blood Cell Traits in African-Americans: An Electronic Medical Record-based Genome-Wide Association Study |
title_full_unstemmed | Genetic Variants That Confer Resistance to Malaria Are Associated with Red Blood Cell Traits in African-Americans: An Electronic Medical Record-based Genome-Wide Association Study |
title_short | Genetic Variants That Confer Resistance to Malaria Are Associated with Red Blood Cell Traits in African-Americans: An Electronic Medical Record-based Genome-Wide Association Study |
title_sort | genetic variants that confer resistance to malaria are associated with red blood cell traits in african-americans: an electronic medical record-based genome-wide association study |
topic | Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704235/ https://www.ncbi.nlm.nih.gov/pubmed/23696099 http://dx.doi.org/10.1534/g3.113.006452 |
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