ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response

被引：75

作者：

Adeyemo, Adebowale A. ^{[1
]}

Zaghloul, Norann A. ^{[2
,3
]}

Chen, Guanjie ^{[1
]}

Doumatey, Ayo P. ^{[1
]}

Leitch, Carmen C. ^{[2
]}

Hostelley, Timothy L. ^{[2
]}

Nesmith, Jessica E. ^{[2
]}

Zhou, Jie ^{[1
]}

Bentley, Amy R. ^{[1
]}

Shriner, Daniel ^{[1
]}

Fasanmade, Olufemi ^{[4
]}

Okafor, Godfrey ^{[5
]}

Eghan, Benjamin, Jr. ^{[6
]}

Agyenim-Boateng, Kofi ^{[6
]}

Chandrasekharappa, Settara ^{[7
]}

Adeleye, Jokotade ^{[8
]}

Balogun, William ^{[8
]}

Owusu, Samuel ^{[9
]}

Amoah, Albert ^{[9
]}

Acheampong, Joseph ^{[6
]}

Johnson, Thomas ^{[4
]}

Oli, Johnnie ^{[5
]}

Adebamowo, Clement ^{[10
,11
,12
]}

Collins, Francis ^{[14
]}

Dunston, Georgia ^{[15
]}

Rotimi, Charles N. ^{[1
]}

Chen, Ji ^{[16
]}

Sun, Meng ^{[17
]}

Pirie, Fraser ^{[18
]}

Carstensen, Tommy ^{[19
]}

Pomilla, Cristina ^{[16
]}

Young, Elizabeth H. ^{[19
]}

Sandhu, Manjinder ^{[19
]}

Morris, Andrew P. ^{[17
,20
]}

Barroso, Ines ^{[21
]}

McCarthy, Mark, I ^{[13
,17
,22
]}

Mahajan, Anubha ^{[17
]}

Wheeler, Eleanor ^{[16
,21
]}

Motala, Ayesha A. ^{[18
]}

机构：

[1] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA

[2] Univ Maryland, Dept Med, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[3] Univ Maryland, Program Personalized & Genom Med, Sch Med, Baltimore, MD 21201 USA

[4] Univ Lagos, Lagos, Nigeria

[5] Univ Nigeria, Teaching Hosp, Enugu, Nigeria

[6] Univ Sci & Technol, Kumasi, Ghana

[7] NHGRI, NIH, Bethesda, MD 20892 USA

[8] Univ Ibadan, Coll Med, Ibadan, Nigeria

[9] Univ Ghana, Med Sch, Accra, Ghana

[10] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA

[11] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA

[12] Univ Maryland, Sch Med, Greenebaum Comprehens Canc Ctr, Baltimore, MD 21201 USA

[13] Oxford NIHR Biomed Res Ctr, Oxford OX3 7JX, England

[14] NIH, Bldg 10, Bethesda, MD 20892 USA

[15] Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA

[16] Wellcome Sanger Inst, Cambridge C310 1SA, England

[17] Univ Oxford, Wellcorne Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England

[18] Univ KwaZulu Natal, Dept Diabet & Endocrinol, ZA-4013 Durban, South Africa

[19] Univ Cambridge, Dept Med, Cambridge CB2 0QQ, England

[20] Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England

[21] Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge CB2 0QQ, England

[22] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LE, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; SUSCEPTIBILITY GENES; METAANALYSIS; TRAITS; INDIVIDUALS; GLUCOSE; TCF7L2; IMPACT; RISK;

D O I：

10.1038/s41467-019-10967-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 similar to 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 x 10(-9)). Knockdown or genomic knockout of the zebrafish ortholog results in reduction in pancreatic beta-cell number which we demonstrate to be due to increased apoptosis in islets. siRNA transfection of murine Zranb3 in MIN6 beta-cells results in impaired insulin secretion in response to high glucose, implicating Zranb3 in beta-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.

引用

页数：12

共 74 条

[1] What does genomic medicine mean for diverse populations? [J].

Adeyemo, Adebowale ;

Rotimi, Charles .

MOLECULAR GENETICS & GENOMIC MEDICINE, 2014, 2 (01) :3-6

[2] Evaluation of Genome Wide Association Study Associated Type 2 Diabetes Susceptibility Loci in Sub Saharan Africans [J].

Adeyemo, Adebowale A. ;

Tekola-Ayele, Fasil ;

Doumatey, Ayo P. ;

Bentley, Amy R. ;

Chen, Guanjie ;

Huang, Hanxia ;

Zhou, Jie ;

Shriner, Daniel ;

Fasanmade, Olufemi ;

Okafor, Godfrey ;

Eghan, Benjamin, Jr. ;

Agyenim-Boateng, Kofi ;

Adeleye, Jokotade ;

Balogun, Williams ;

Elkahloun, Abdel ;

Chandrasekharappa, Settara ;

Owusu, Samuel ;

Amoah, Albert ;

Acheampong, Joseph ;

Johnson, Thomas ;

Oli, Johnnie ;

Adebamowo, Clement ;

Collins, Francis ;

Dunston, Georgia ;

Rotimi, Charles N. .

FRONTIERS IN GENETICS, 2015, 6

[3] Fast set-based association analysis using summary data from GWAS identifies novel gene loci for human complex traits [J].

Bakshi, Andrew ;

Zhu, Zhihong ;

Vinkhuyzen, Anna A. E. ;

Hill, W. David ;

Mcrae, Allan F. ;

Visscher, Peter M. ;

Yang, Jian .

SCIENTIFIC REPORTS, 2016, 6

[4] Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs [J].

Below, Jennifer E. ;

Parra, Esteban J. ;

Gamazon, Eric R. ;

Torres, Jason ;

Krithika, S. ;

Candille, Sophie ;

Lu, Yingchang ;

Manichakul, Ani ;

Peralta-Romero, Jesus ;

Duan, Qing ;

Li, Yun ;

Morris, Andrew P. ;

Gottesman, Omri ;

Bottinger, Erwin ;

Wang, Xin-Qun ;

Taylor, Kent D. ;

Chen, Y. -D. Ida ;

Rotter, Jerome I. ;

Rich, Stephen S. ;

Loos, Ruth J. F. ;

Tang, Hua ;

Cox, Nancy J. ;

Cruz, Miguel ;

Hanis, Craig L. ;

Valladares-Salgado, Adan .

SCIENTIFIC REPORTS, 2016, 6

[5] Diversity and inclusion in genomic research: why the uneven progress? [J].

Bentley A.R. ;

Callier S. ;

Rotimi C.N. .

Journal of Community Genetics, 2017, 8 (4) :255-266

[6] TCF7L2 is associated with type 2 diabetes in nonobese individuals from Tunisia [J].

Bouhaha, R. ;

Choquet, H. ;

Meyre, D. ;

Kamoun, H. Abid ;

Ennafaa, H. ;

Baroudi, T. ;

Sassi, R. ;

Vaxillaire, M. ;

Elgaaied, A. ;

Froguel, P. ;

Cauchi, S. .

PATHOLOGIE BIOLOGIE, 2010, 58 (06) :426-429

[7]

Bretherton CS, 1999, J CLIMATE, V12, P1990, DOI 10.1175/1520-0442(1999)012<1990:TENOSD>2.0.CO

[8]

[9] Genomics for the world [J].

Bustamante, Carlos D. ;

Burchard, Esteban Gonzalez ;

De La Vega, Francisco M. .

NATURE, 2011, 475 (7355) :163-165

[10] European genetic variants associated with type 2 diabetes in North African Arabs [J].

Cauchi, S. ;

Ezzidi, I. ;

El Achhab, Y. ;

Mtiraoui, N. ;

Chaieb, L. ;

Salah, D. ;

Nejjari, C. ;

Labrune, Y. ;

Yengo, L. ;

Beury, D. ;

Vaxillaire, M. ;

Mahjoub, T. ;

Chikri, M. ;

Froguel, P. .

DIABETES & METABOLISM, 2012, 38 (04) :316-323

← 1 2 3 4 5 6 7 8 →