ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response
| Autor: | Kofi Agyenim-Boateng, Ayo P. Doumatey, Adebowale Adeyemo, Charles N. Rotimi, Settara C. Chandrasekharappa, Albert G.B. Amoah, Norann A. Zaghloul, Thomas Johnson, William Balogun, Daniel Shriner, Joseph Acheampong, Guanjie Chen, Jie Zhou, Olufemi Fasanmade, Clement Adebamowo, Benjamin A. Eghan, South Africa Zulu Type Diabetes Case-Control Study, Jokotade Adeleye, Jessica E. Nesmith, Francis S. Collins, Samuel Owusu, Timothy L. Hostelley, Carmen C. Leitch, Johnnie Oli, Godfrey Okafor, Georgia M. Dunston, Amy R. Bentley |
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| Přispěvatelé: | Adeyemo, Adebowale A [0000-0002-3105-3231], Chen, Guanjie [0000-0002-5745-5618], Bentley, Amy R [0000-0002-0827-9101], Rotimi, Charles N [0000-0001-5759-053X], Apollo - University of Cambridge Repository |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Blood Glucose Male CRISPR-Cas9 genome editing endocrine system diseases medicine.medical_treatment General Physics and Astronomy Apoptosis 02 engineering and technology Type 2 diabetes Ghana Genome-wide association studies Gene Knockout Techniques Mice Africa Northern Insulin-Secreting Cells Insulin RNA Small Interfering lcsh:Science Zebrafish Genetics Gene Editing Developing world education.field_of_study Multidisciplinary Homozygote Middle Aged 021001 nanoscience & nanotechnology 3. Good health Female Beta cell 0210 nano-technology Transcription Factor 7-Like 2 Protein Genotype Science Population Nigeria Single-nucleotide polymorphism Locus (genetics) Biology Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Diabetes mellitus medicine SNP Animals Humans Genetic Predisposition to Disease education Genetic Association Studies Base Sequence DNA Helicases nutritional and metabolic diseases General Chemistry medicine.disease Kenya Disease Models Animal 030104 developmental biology Glucose Diabetes Mellitus Type 2 Mutation lcsh:Q CRISPR-Cas Systems Transcriptome |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019) |
| ISSN: | 2041-1723 |
| Popis: | Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report a genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyze ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. We identify a previously-unreported genome-wide significant locus: ZRANB3 (Zinc Finger RANBP2-Type Containing 3, lead SNP p = 2.831 × 10−9). Knockdown or genomic knockout of the zebrafish ortholog results in reduction in pancreatic β-cell number which we demonstrate to be due to increased apoptosis in islets. siRNA transfection of murine Zranb3 in MIN6 β-cells results in impaired insulin secretion in response to high glucose, implicating Zranb3 in β-cell functional response to high glucose conditions. We also show transferability in our study of 32 established T2D loci. Our findings advance understanding of the genetics of T2D in non-European ancestry populations. Type 2 diabetes (T2D) is prevalent in populations worldwide, however, mostly studied in European and mixed-ancestry populations. Here, the authors perform a genome-wide association study for T2D in over 5,000 sub-Saharan Africans and identify a locus, ZRANB3, that is specific for this population. |
| Databáze: | OpenAIRE |
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