title: Evaluation of Genome Wide Association Study Associated Type 2 Diabetes Susceptibility Loci in Sub Saharan Africans.
abstract: Genome wide association studies (GWAS) for type 2 diabetes (T2D) undertaken in European and Asian ancestry populations have yielded dozens of robustly associated loci. However, the genomics of T2D remains largely understudied in sub-Saharan Africa (SSA), where rates of T2D are increasing dramatically and where the environmental background is quite different than in these previous studies. Here, we evaluate 106 reported T2D GWAS loci in continental Africans. We tested each of these SNPs, and SNPs in linkage disequilibrium (LD) with these index SNPs, for an association with T2D in order to assess transferability and to fine map the loci leveraging the generally reduced LD of African genomes. The study included 1775 unrelated Africans (1035 T2D cases, 740 controls; mean age 54 years; 59% female) enrolled in Nigeria, Ghana, and Kenya as part of the Africa America Diabetes Mellitus (AADM) study. All samples were genotyped on the Affymetrix Axiom PanAFR SNP array. Forty-one of the tested loci showed transferability to this African sample (p < 0.05, same direction of effect), 11 at the exact reported SNP and 30 others at SNPs in LD with the reported SNP (after adjustment for the number of tested SNPs). TCF7L2 SNP rs7903146 was the most significant locus in this study (p = 1.61 × 10(-8)). Most of the loci that showed transferability were successfully fine-mapped, i.e., localized to smaller haplotypes than in the original reports. The findings indicate that the genetic architecture of T2D in SSA is characterized by several risk loci shared with non-African ancestral populations and that data from African populations may facilitate fine mapping of risk loci. The study provides an important resource for meta-analysis of African ancestry populations and transferability of novel loci.
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA.
authors.forename: Adebowale A
authors.initials: AA
authors.lastname: Adeyemo
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA.
authors.forename: Fasil
authors.initials: F
authors.lastname: Tekola-Ayele
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA.
authors.forename: Ayo P
authors.initials: AP
authors.lastname: Doumatey
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Bentley
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA.
authors.forename: Guanjie
authors.initials: G
authors.lastname: Chen
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA.
authors.forename: Hanxia
authors.initials: H
authors.lastname: Huang
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Shriner
authors.affiliation: Department of Medicine, University of Lagos Lagos, Nigeria.
authors.forename: Olufemi
authors.initials: O
authors.lastname: Fasanmade
authors.affiliation: Department of Medicine, University of Nigeria Teaching Hospital Enugu, Nigeria.
authors.forename: Godfrey
authors.initials: G
authors.lastname: Okafor
authors.affiliation: Department of Medicine, University of Science and Technology Kumasi, Ghana.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Eghan
authors.affiliation: Department of Medicine, University of Science and Technology Kumasi, Ghana.
authors.forename: Kofi
authors.initials: K
authors.lastname: Agyenim-Boateng
authors.affiliation: Department of Medicine, College of Medicine, University of Ibadan Ibadan, Nigeria.
authors.forename: Jokotade
authors.initials: J
authors.lastname: Adeleye
authors.affiliation: Department of Medicine, College of Medicine, University of Ibadan Ibadan, Nigeria.
authors.forename: Williams
authors.initials: W
authors.lastname: Balogun
authors.affiliation: National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA.
authors.forename: Abdel
authors.initials: A
authors.lastname: Elkahloun
authors.affiliation: National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA.
authors.forename: Settara
authors.initials: S
authors.lastname: Chandrasekharappa
authors.affiliation: Department of Medicine and Therapeutics, University of Ghana Medical School Accra, Ghana.
authors.forename: Samuel
authors.initials: S
authors.lastname: Owusu
authors.affiliation: Department of Medicine and Therapeutics, University of Ghana Medical School Accra, Ghana.
authors.forename: Albert
authors.initials: A
authors.lastname: Amoah
authors.affiliation: Department of Medicine, University of Science and Technology Kumasi, Ghana.
authors.forename: Joseph
authors.initials: J
authors.lastname: Acheampong
authors.affiliation: Department of Medicine, University of Lagos Lagos, Nigeria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Johnson
authors.affiliation: Department of Medicine, University of Nigeria Teaching Hospital Enugu, Nigeria.
authors.forename: Johnnie
authors.initials: J
authors.lastname: Oli
authors.affiliation: Institute of Human Virology, School of Medicine, University of Maryland Baltimore, MD, USA.
authors.forename: Clement
authors.initials: C
authors.lastname: Adebamowo
authors.affiliation: National Institutes of Health Bethesda, MD, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Collins
authors.affiliation: National Human Genome Center at Howard University Washington, DC, USA.
authors.forename: Georgia
authors.initials: G
authors.lastname: Dunston
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health Bethesda, MD, USA.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Rotimi
keywords: fine-mapping; genetic association; replication; sub Saharan Africa; type 2 diabetes