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"""""""". 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) using the Illumina Custom infinium II BeadChip. 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. This procedure increased the number of SNPs from 1,496 to over 22,000 resulting in a much denser genetic map ( 1kb density from about 11kb). We have completed analyses of this project and we have identified exciting novel genetic variants for obesity and diabetes that promises to shed light on the pathophysiology of these human diseases. The manuscripts describing these findings are complete and we are awaiting the results of the replication projects in other populations. The initial results were presented recently in San Francisco during the 2008 American Diabetes Association annual meeting. 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 for Hypertension Genes in African Americans: The CRGGH lab is using the admixture mapping approach to identify regions of the genome that may harbor hypertension susceptibility genes in African Americans. We have genotyped a panel of over 3,000 ancestry informative markers in a well-characterized cohort of African Americans enrolled from the Washington, D.C. metropolitan area. This data is being analyzed by investigators at the CRGGH lab. Identified susceptibility loci will be subjected to fine mapping using a very high density SNP panel selected from the HapMap database. In combination with bioinformatics methods, the CRGGH lab will use the data from the fine-mapping studies to identify genes to be resequenced for mutation detection and replication studies in multiple populations. Comprehensive Candidate Gene Approach to Identify Hypertension Susceptibility Genes in African Americans and African Populations: The CRGGH lab has completed a large-scale candidate genes study for hypertension (HTN) in African Americans and multiple African populations. A total number of 1598 subjects (comprising 1002 African Americans and 562 West Africans) have been genotyped using Illuminas custom SNP GoldenGate genotyping platform. Given the poor consistency of candidate gene studies for HTN, we gave careful thought to the selection of genetic variants represented in the final custom panel of 768 SNPs. Investigators in the center are using the case-control association strategy, under various genetic models, to identify susceptibility variants to HTN. Genetics of Podoconiosis: In collaboration with scientists from Ethiopia and the UK, CRGGH investigators are conducting the first genetic epidemiology study that will attempt 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. One of the striking features of podoconiosis is that only a small proportion of individuals who are exposed to red clay develop disease. The field work for this project is complete and DNA samples were sent to a commercial genotyping facility for genome-wide SNP genotyping. A total of 198 cases and 203 controls were genotyped using the Illumina HumanHap 610 Bead Chip which contains over 600,000 single nucleotide polymorphisms (SNPs). Resulting genome-wide association data is being analyzed by our PhD student (Fasil Tekola) under the supervision of Drs. Adeyemo and Rotimi. We recently published a manuscript detailing the informed consent process for this study entitled """"""""Tailoring consent to context: designing an appropriate consent process for a biomedical study in a low income setting"""""""" in the journal PLoS Negl Trop Dis. 2009 Jul 21;3(7). The Black Women Health Study (BWHS): The CRGGH lab is collaborating with Boston University to develop a project to conduct a genome-wide association study in 4,000 African American women (2,000 cases of diabetes and 2,000 controls) in the BWHS. The BWHS is a national longitudinal cohort of women assembled in 1995 to study causes of illness in black women. It includes 59,000 women aged 21-69 at baseline. Dr. Rotimis lab was responsible for receiving, isolating and tracking DNA samples on these women. Over 25,000 DNA samples have been processed to date. An R01 grant has been submitted by our collaborators to NIDDK to conduct a GWAS in 2000 cases of diabetes and 2000 controls. We recently submitted a manuscript titled """"""""Novel region in the FGFR2 gene is associated with breast cancer in African American women"""""""" for review.
| 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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