Genome Wide Association Studies (GWAS): In collaboration with investigators at the Coriell Institute for Biomedical Research, the CRGGH lab has successfully completed a genome-wide scan of over 2000 African Americans using the Affymetrix Genome-Wide Human SNP Array 6.0 with 1.8 million genetic markers ( equal number of SNPs and CNVs). Investigators at the center are currently analyzing generated data on multiple phenotypes including obesity, hypertension, diabetes and height. We recently published the analyses of the hypertension and blood pressure findings in the journal PLOS Genetics 2009 Jul;5(7)- """"""""A genome-wide association study of hypertension and blood pressure in African Americans"""""""". CRGGH has received funding to conduct the first GWAS on 2,400 Africans with type 2 diabetes and equal number of controls. It is anticipated that genotyping data will be available for analysis in January 2012. The center is conducting whole-exome sequencing of 20 African American families with multiple affected persons and 20 West African families with at least 4 affected family members. It is anticipated that sequence data will be available in October 2011. The CRGGH lab has successfully genotyped several African ancestry populations using the Affymetrix DMET chip to study the pharmacogenomics of drug metabolizing enzymes. Data analysis is ongoing. Fine-mapping of Diabetes Genes: The CRGGH lab is conducting fine mapping of a linkage region on chromosome 5q22-5q31 (109055750 128436401 base pairs). Genotyping for this project was conducted by the Center for Inherited Disease Research (CIDR). A total of 1,536 SNPs were attempted and 1,496 SNPs were released. In addition, we used the imputation procedure to impute genotypes using the HapMap release #22 in 60 YRI (Yoruba) founders. Analysis is ongoing. We have ongoing large-scale genetic epidemiology studies that are designed to shed light on the complex interaction between genetic and environmental factors in the etiology of diabetes and associated complications in multiple African countries (Nigeria Ghana and Kenya), in Suizhou, China and among African Americans from Washington, DC and Mexican Americans from Houston, Texas. Admixture Mapping in African Americans: The CRGGH lab is using the admixture mapping approach to identify regions of the genome that may harbor susceptibility genes in African Americans for several traits. We recently published a review article on admixture mapping (Genome Biol. 2011 May 30;12(5):223). The center is currently engaged in multiple admixture mapping projects. Genetics of Podoconiosis: In collaboration with scientists from Ethiopia and the UK, CRGGH investigators have completed the first GWAS to unravel the complex interaction between genes and environment in the etiology of podoconiosis (endemic non-filarial elephantiasis). Podoconiosis is a geochemical disease occurring in individuals exposed to red clay soil derived from alkalic volcanic rock. The GWAS analysis is complete and manuscript is under review in NEJM.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2011
Total Cost
$3,659,362
Indirect Cost
Name
National Human Genome Research Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Shriner, Daniel; Rotimi, Charles N (2018) Genetic history of Chad. Am J Phys Anthropol 167:804-812
Shriner, Daniel; Tekola-Ayele, Fasil; Adeyemo, Adebowale et al. (2018) Genetic Ancestry of Hadza and Sandawe Peoples Reveals Ancient Population Structure in Africa. Genome Biol Evol 10:875-882
Shriner, Daniel (2018) Re-analysis of Whole Genome Sequence Data From 279 Ancient Eurasians Reveals Substantial Ancestral Heterogeneity. Front Genet 9:268
Shriner, Daniel; Rotimi, Charles N (2018) Whole-Genome-Sequence-Based Haplotypes Reveal Single Origin of the Sickle Allele during the Holocene Wet Phase. Am J Hum Genet 102:547-556
Bentley, Amy R; Callier, Shawneequa; Rotimi, Charles N (2017) Diversity and inclusion in genomic research: why the uneven progress? J Community Genet 8:255-266
Atun, Rifat; Davies, Justine I; Gale, Edwin A M et al. (2017) Diabetes in sub-Saharan Africa: from clinical care to health policy. Lancet Diabetes Endocrinol 5:622-667
Bentley, Amy R; Rotimi, Charles N (2017) Interethnic Differences in Serum Lipids and Implications for Cardiometabolic Disease Risk in African Ancestry Populations. Glob Heart 12:141-150
Faruque, Mezbah U; Chen, Guanjie; Doumatey, Ayo P et al. (2017) Transferability of genome-wide associated loci for asthma in African Americans. J Asthma 54:1-8
Baker, J L; Shriner, D; Bentley, A R et al. (2017) Pharmacogenomic implications of the evolutionary history of infectious diseases in Africa. Pharmacogenomics J 17:112-120
Ormond, Kelly E; Mortlock, Douglas P; Scholes, Derek T et al. (2017) Human Germline Genome Editing. Am J Hum Genet 101:167-176

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