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Admixture Mapping and Subsequent Fine-Mapping Suggests a Biologically Relevant and Novel Association on Chromosome 11 for Type 2 Diabetes in African Americans

Type 2 diabetes (T2D) is a complex metabolic disease that disproportionately affects African Americans. Genome-wide association studies (GWAS) have identified several loci that contribute to T2D in European Americans, but few studies have been performed in admixed populations. We first performed a G...

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Autores principales: Jeff, Janina M., Armstrong, Loren L., Ritchie, Marylyn D., Denny, Joshua C., Kho, Abel N., Basford, Melissa A., Wolf, Wendy A., Pacheco, Jennifer A., Li, Rongling, Chisholm, Rex L., Roden, Dan M., Hayes, M. Geoffrey, Crawford, Dana C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940426/
https://www.ncbi.nlm.nih.gov/pubmed/24595071
http://dx.doi.org/10.1371/journal.pone.0086931
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author Jeff, Janina M.
Armstrong, Loren L.
Ritchie, Marylyn D.
Denny, Joshua C.
Kho, Abel N.
Basford, Melissa A.
Wolf, Wendy A.
Pacheco, Jennifer A.
Li, Rongling
Chisholm, Rex L.
Roden, Dan M.
Hayes, M. Geoffrey
Crawford, Dana C.
author_facet Jeff, Janina M.
Armstrong, Loren L.
Ritchie, Marylyn D.
Denny, Joshua C.
Kho, Abel N.
Basford, Melissa A.
Wolf, Wendy A.
Pacheco, Jennifer A.
Li, Rongling
Chisholm, Rex L.
Roden, Dan M.
Hayes, M. Geoffrey
Crawford, Dana C.
author_sort Jeff, Janina M.
collection PubMed
description Type 2 diabetes (T2D) is a complex metabolic disease that disproportionately affects African Americans. Genome-wide association studies (GWAS) have identified several loci that contribute to T2D in European Americans, but few studies have been performed in admixed populations. We first performed a GWAS of 1,563 African Americans from the Vanderbilt Genome-Electronic Records Project and Northwestern University NUgene Project as part of the electronic Medical Records and Genomics (eMERGE) network. We successfully replicate an association in TCF7L2, previously identified by GWAS in this African American dataset. We were unable to identify novel associations at p<5.0×10(−8) by GWAS. Using admixture mapping as an alternative method for discovery, we performed a genome-wide admixture scan that suggests multiple candidate genes associated with T2D. One finding, TCIRG1, is a T-cell immune regulator expressed in the pancreas and liver that has not been previously implicated for T2D. We performed subsequent fine-mapping to further assess the association between TCIRG1 and T2D in >5,000 African Americans. We identified 13 independent associations between TCIRG1, CHKA, and ALDH3B1 genes on chromosome 11 and T2D. Our results suggest a novel region on chromosome 11 identified by admixture mapping is associated with T2D in African Americans.
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spelling pubmed-39404262014-03-06 Admixture Mapping and Subsequent Fine-Mapping Suggests a Biologically Relevant and Novel Association on Chromosome 11 for Type 2 Diabetes in African Americans Jeff, Janina M. Armstrong, Loren L. Ritchie, Marylyn D. Denny, Joshua C. Kho, Abel N. Basford, Melissa A. Wolf, Wendy A. Pacheco, Jennifer A. Li, Rongling Chisholm, Rex L. Roden, Dan M. Hayes, M. Geoffrey Crawford, Dana C. PLoS One Research Article Type 2 diabetes (T2D) is a complex metabolic disease that disproportionately affects African Americans. Genome-wide association studies (GWAS) have identified several loci that contribute to T2D in European Americans, but few studies have been performed in admixed populations. We first performed a GWAS of 1,563 African Americans from the Vanderbilt Genome-Electronic Records Project and Northwestern University NUgene Project as part of the electronic Medical Records and Genomics (eMERGE) network. We successfully replicate an association in TCF7L2, previously identified by GWAS in this African American dataset. We were unable to identify novel associations at p<5.0×10(−8) by GWAS. Using admixture mapping as an alternative method for discovery, we performed a genome-wide admixture scan that suggests multiple candidate genes associated with T2D. One finding, TCIRG1, is a T-cell immune regulator expressed in the pancreas and liver that has not been previously implicated for T2D. We performed subsequent fine-mapping to further assess the association between TCIRG1 and T2D in >5,000 African Americans. We identified 13 independent associations between TCIRG1, CHKA, and ALDH3B1 genes on chromosome 11 and T2D. Our results suggest a novel region on chromosome 11 identified by admixture mapping is associated with T2D in African Americans. Public Library of Science 2014-03-03 /pmc/articles/PMC3940426/ /pubmed/24595071 http://dx.doi.org/10.1371/journal.pone.0086931 Text en © 2014 Jeff et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Jeff, Janina M.
Armstrong, Loren L.
Ritchie, Marylyn D.
Denny, Joshua C.
Kho, Abel N.
Basford, Melissa A.
Wolf, Wendy A.
Pacheco, Jennifer A.
Li, Rongling
Chisholm, Rex L.
Roden, Dan M.
Hayes, M. Geoffrey
Crawford, Dana C.
Admixture Mapping and Subsequent Fine-Mapping Suggests a Biologically Relevant and Novel Association on Chromosome 11 for Type 2 Diabetes in African Americans
title Admixture Mapping and Subsequent Fine-Mapping Suggests a Biologically Relevant and Novel Association on Chromosome 11 for Type 2 Diabetes in African Americans
title_full Admixture Mapping and Subsequent Fine-Mapping Suggests a Biologically Relevant and Novel Association on Chromosome 11 for Type 2 Diabetes in African Americans
title_fullStr Admixture Mapping and Subsequent Fine-Mapping Suggests a Biologically Relevant and Novel Association on Chromosome 11 for Type 2 Diabetes in African Americans
title_full_unstemmed Admixture Mapping and Subsequent Fine-Mapping Suggests a Biologically Relevant and Novel Association on Chromosome 11 for Type 2 Diabetes in African Americans
title_short Admixture Mapping and Subsequent Fine-Mapping Suggests a Biologically Relevant and Novel Association on Chromosome 11 for Type 2 Diabetes in African Americans
title_sort admixture mapping and subsequent fine-mapping suggests a biologically relevant and novel association on chromosome 11 for type 2 diabetes in african americans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940426/
https://www.ncbi.nlm.nih.gov/pubmed/24595071
http://dx.doi.org/10.1371/journal.pone.0086931
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