Admixture mapping and subsequent fine-mapping suggests a biologically relevant and novel association on chromosome 11 for type 2 diabetes in African Americans

Janina M. Jeff, Loren L. Armstrong, Marylyn Deriggi Ritchie, Joshua C. Denny, Abel N. Kho, Melissa A. Basford, Wendy A. Wolf, Jennifer A. Pacheco, Rongling Li, Rex L. Chisholm, Dan M. Roden, M. Geoffrey Hayes, Dana C. Crawford

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere86931
JournalPloS one
Volume9
Issue number3
DOIs
StatePublished - Mar 3 2014

Fingerprint

Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 2
African Americans
Chromosomes
Medical problems
noninsulin-dependent diabetes mellitus
Type 2 Diabetes Mellitus
Genes
Genome-Wide Association Study
chromosomes
electronics
Electronic medical equipment
Electronic Health Records
Metabolic Diseases
metabolic diseases
Genomics
Genome
genomics
loci
genome

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Jeff, Janina M. ; Armstrong, Loren L. ; Ritchie, Marylyn Deriggi ; Denny, Joshua C. ; Kho, Abel N. ; Basford, Melissa A. ; Wolf, Wendy A. ; Pacheco, Jennifer A. ; Li, Rongling ; Chisholm, Rex L. ; Roden, Dan M. ; Geoffrey Hayes, M. ; 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. In: PloS one. 2014 ; Vol. 9, No. 3.
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abstract = "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.",
author = "Jeff, {Janina M.} and Armstrong, {Loren L.} and Ritchie, {Marylyn Deriggi} and Denny, {Joshua C.} and Kho, {Abel N.} and Basford, {Melissa A.} and Wolf, {Wendy A.} and Pacheco, {Jennifer A.} and Rongling Li and Chisholm, {Rex L.} and Roden, {Dan M.} and {Geoffrey Hayes}, M. and Crawford, {Dana C.}",
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Jeff, JM, Armstrong, LL, Ritchie, MD, Denny, JC, Kho, AN, Basford, MA, Wolf, WA, Pacheco, JA, Li, R, Chisholm, RL, Roden, DM, Geoffrey Hayes, M & Crawford, DC 2014, 'Admixture mapping and subsequent fine-mapping suggests a biologically relevant and novel association on chromosome 11 for type 2 diabetes in African Americans', PloS one, vol. 9, no. 3, e86931. https://doi.org/10.1371/journal.pone.0086931

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 Deriggi; Denny, Joshua C.; Kho, Abel N.; Basford, Melissa A.; Wolf, Wendy A.; Pacheco, Jennifer A.; Li, Rongling; Chisholm, Rex L.; Roden, Dan M.; Geoffrey Hayes, M.; Crawford, Dana C.

In: PloS one, Vol. 9, No. 3, e86931, 03.03.2014.

Research output: Contribution to journalArticle

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T1 - Admixture mapping and subsequent fine-mapping suggests a biologically relevant and novel association on chromosome 11 for type 2 diabetes in African Americans

AU - Jeff, Janina M.

AU - Armstrong, Loren L.

AU - Ritchie, Marylyn Deriggi

AU - Denny, Joshua C.

AU - Kho, Abel N.

AU - Basford, Melissa A.

AU - Wolf, Wendy A.

AU - Pacheco, Jennifer A.

AU - Li, Rongling

AU - Chisholm, Rex L.

AU - Roden, Dan M.

AU - Geoffrey Hayes, M.

AU - Crawford, Dana C.

PY - 2014/3/3

Y1 - 2014/3/3

N2 - 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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