PUBLICATION
ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response
- Authors
- Adeyemo, A.A., Zaghloul, N.A., Chen, G., Doumatey, A.P., Leitch, C.C., Hostelley, T.L., Nesmith, J.E., Zhou, J., Bentley, A.R., Shriner, D., Fasanmade, O., Okafor, G., Eghan, B., Agyenim-Boateng, K., Chandrasekharappa, S., Adeleye, J., Balogun, W., Owusu, S., Amoah, A., Acheampong, J., Johnson, T., Oli, J., Adebamowo, C., South Africa Zulu Type 2 Diabetes Case-Control Study, Collins, F., Dunston, G., Rotimi, C.N.
- ID
- ZDB-PUB-190724-12
- Date
- 2019
- Source
- Nature communications 10: 3195 (Journal)
- Registered Authors
- Chandrasekharappa, Settara, Rotimi, Charles, Zaghloul, Norann A.
- Keywords
- none
- Datasets
- GEO:GSE125354
- MeSH Terms
-
- Africa, Northern
- Animals
- Apoptosis
- Base Sequence
- Blood Glucose
- CRISPR-Cas Systems
- DNA Helicases/genetics*
- DNA Helicases/metabolism*
- Diabetes Mellitus, Type 2/genetics*
- Disease Models, Animal
- Female
- Gene Editing
- Gene Knockout Techniques
- Genetic Association Studies*
- Genetic Predisposition to Disease/genetics*
- Genotype
- Ghana
- Glucose/metabolism
- Homozygote
- Humans
- Insulin/metabolism*
- Insulin-Secreting Cells/metabolism*
- Kenya
- Male
- Mice
- Middle Aged
- Mutation
- Nigeria
- Polymorphism, Single Nucleotide
- RNA, Small Interfering
- Transcription Factor 7-Like 2 Protein/genetics
- Transcriptome
- Zebrafish
- PubMed
- 31324766 Full text @ Nat. Commun.
Citation
Adeyemo, A.A., Zaghloul, N.A., Chen, G., Doumatey, A.P., Leitch, C.C., Hostelley, T.L., Nesmith, J.E., Zhou, J., Bentley, A.R., Shriner, D., Fasanmade, O., Okafor, G., Eghan, B., Agyenim-Boateng, K., Chandrasekharappa, S., Adeleye, J., Balogun, W., Owusu, S., Amoah, A., Acheampong, J., Johnson, T., Oli, J., Adebamowo, C., South Africa Zulu Type 2 Diabetes Case-Control Study, Collins, F., Dunston, G., Rotimi, C.N. (2019) ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response. Nature communications. 10:3195.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping