title: Admixture mapping and subsequent fine-mapping suggests a biologically relevant and novel association on chromosome 11 for type 2 diabetes in African Americans.
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.
authors.affiliation: Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Janina M
authors.initials: JM
authors.lastname: Jeff
authors.affiliation: Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Loren L
authors.initials: LL
authors.lastname: Armstrong
authors.affiliation: Center for System Genomics, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.affiliation: Department of Medicine, Division of Clinical Pharmacology,Vanderbilt University, Nashville, Tennessee, United States of America; Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.affiliation: Division of General Internal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Abel N
authors.initials: AN
authors.lastname: Kho
authors.affiliation: Office of Personalized Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Basford
authors.affiliation: Division of Genetics, Children's Hospital Boston, Boston, Massachusetts, United States of America.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Wolf
authors.affiliation: Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Pacheco
authors.affiliation: Office of Population Genomics, National Human Genome Research Institute, Bethesda, Maryland, United States of America.
authors.forename: Rongling
authors.initials: R
authors.lastname: Li
authors.affiliation: Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Rex L
authors.initials: RL
authors.lastname: Chisholm
authors.affiliation: Department of Medicine, Division of Clinical Pharmacology,Vanderbilt University, Nashville, Tennessee, United States of America; Office of Personalized Medicine, Vanderbilt University, Nashville, Tennessee, United States of America; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America; Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: M Geoffrey
authors.initials: MG
authors.lastname: Hayes
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
mesh_terms: D044383:Black People / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D002880:Chromosomes, Human, Pair 11; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D001741:Black or African American