title: Transferability and fine mapping of type 2 diabetes loci in African Americans: the Candidate Gene Association Resource Plus Study.
abstract: Type 2 diabetes (T2D) disproportionally affects African Americans (AfA) but, to date, genetic variants identified from genome-wide association studies (GWAS) are primarily from European and Asian populations. We examined the single nucleotide polymorphism (SNP) and locus transferability of 40 reported T2D loci in six AfA GWAS consisting of 2,806 T2D case subjects with or without end-stage renal disease and 4,265 control subjects from the Candidate Gene Association Resource Plus Study. Our results revealed that seven index SNPs at the TCF7L2, KLF14, KCNQ1, ADCY5, CDKAL1, JAZF1, and GCKR loci were significantly associated with T2D (P < 0.05). The strongest association was observed at TCF7L2 rs7903146 (odds ratio [OR] 1.30; P = 6.86 × 10⁻⁸). Locus-wide analysis demonstrated significant associations (P(emp) < 0.05) at regional best SNPs in the TCF7L2, KLF14, and HMGA2 loci as well as suggestive signals in KCNQ1 after correction for the effective number of SNPs at each locus. Of these loci, the regional best SNPs were in differential linkage disequilibrium (LD) with the index and adjacent SNPs. Our findings suggest that some loci discovered in prior reports affect T2D susceptibility in AfA with similar effect sizes. The reduced and differential LD pattern in AfA compared with European and Asian populations may facilitate fine mapping of causal variants at loci shared across populations.
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. mng@wakehealth.edu
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.forename: Latchezar
authors.initials: L
authors.lastname: Dimitrov
authors.forename: Jianzhao
authors.initials: J
authors.lastname: Xu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Rasmussen-Torvik
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Zmuda
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Patel
authors.forename: Errol D
authors.initials: ED
authors.lastname: Crook
authors.forename: Mario
authors.initials: M
authors.lastname: Sims
authors.forename: Yii-Der I
authors.initials: YD
authors.lastname: Chen
authors.forename: Alain G
authors.initials: AG
authors.lastname: Bertoni
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D001741:Black or African American; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics* / Q000378:metabolism; D014481:United States
chemical_list: C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein