Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.
Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In...
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Public Library of Science (PLoS)
2014-08-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1004517 |
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| author | Maggie C Y Ng Daniel Shriner Brian H Chen Jiang Li Wei-Min Chen Xiuqing Guo Jiankang Liu Suzette J Bielinski Lisa R Yanek Michael A Nalls Mary E Comeau Laura J Rasmussen-Torvik Richard A Jensen Daniel S Evans Yan V Sun Ping An Sanjay R Patel Yingchang Lu Jirong Long Loren L Armstrong Lynne Wagenknecht Lingyao Yang Beverly M Snively Nicholette D Palmer Poorva Mudgal Carl D Langefeld Keith L Keene Barry I Freedman Josyf C Mychaleckyj Uma Nayak Leslie J Raffel Mark O Goodarzi Y-D Ida Chen Herman A Taylor Adolfo Correa Mario Sims David Couper James S Pankow Eric Boerwinkle Adebowale Adeyemo Ayo Doumatey Guanjie Chen Rasika A Mathias Dhananjay Vaidya Andrew B Singleton Alan B Zonderman Robert P Igo John R Sedor FIND Consortium Edmond K Kabagambe David S Siscovick Barbara McKnight Kenneth Rice Yongmei Liu Wen-Chi Hsueh Wei Zhao Lawrence F Bielak Aldi Kraja Michael A Province Erwin P Bottinger Omri Gottesman Qiuyin Cai Wei Zheng William J Blot William L Lowe Jennifer A Pacheco Dana C Crawford eMERGE Consortium DIAGRAM Consortium Elin Grundberg MuTHER Consortium Stephen S Rich M Geoffrey Hayes Xiao-Ou Shu Ruth J F Loos Ingrid B Borecki Patricia A Peyser Steven R Cummings Bruce M Psaty Myriam Fornage Sudha K Iyengar Michele K Evans Diane M Becker W H Linda Kao James G Wilson Jerome I Rotter Michèle M Sale Simin Liu Charles N Rotimi Donald W Bowden MEta-analysis of type 2 DIabetes in African Americans Consortium |
| author_facet | Maggie C Y Ng Daniel Shriner Brian H Chen Jiang Li Wei-Min Chen Xiuqing Guo Jiankang Liu Suzette J Bielinski Lisa R Yanek Michael A Nalls Mary E Comeau Laura J Rasmussen-Torvik Richard A Jensen Daniel S Evans Yan V Sun Ping An Sanjay R Patel Yingchang Lu Jirong Long Loren L Armstrong Lynne Wagenknecht Lingyao Yang Beverly M Snively Nicholette D Palmer Poorva Mudgal Carl D Langefeld Keith L Keene Barry I Freedman Josyf C Mychaleckyj Uma Nayak Leslie J Raffel Mark O Goodarzi Y-D Ida Chen Herman A Taylor Adolfo Correa Mario Sims David Couper James S Pankow Eric Boerwinkle Adebowale Adeyemo Ayo Doumatey Guanjie Chen Rasika A Mathias Dhananjay Vaidya Andrew B Singleton Alan B Zonderman Robert P Igo John R Sedor FIND Consortium Edmond K Kabagambe David S Siscovick Barbara McKnight Kenneth Rice Yongmei Liu Wen-Chi Hsueh Wei Zhao Lawrence F Bielak Aldi Kraja Michael A Province Erwin P Bottinger Omri Gottesman Qiuyin Cai Wei Zheng William J Blot William L Lowe Jennifer A Pacheco Dana C Crawford eMERGE Consortium DIAGRAM Consortium Elin Grundberg MuTHER Consortium Stephen S Rich M Geoffrey Hayes Xiao-Ou Shu Ruth J F Loos Ingrid B Borecki Patricia A Peyser Steven R Cummings Bruce M Psaty Myriam Fornage Sudha K Iyengar Michele K Evans Diane M Becker W H Linda Kao James G Wilson Jerome I Rotter Michèle M Sale Simin Liu Charles N Rotimi Donald W Bowden MEta-analysis of type 2 DIabetes in African Americans Consortium |
| author_sort | Maggie C Y Ng |
| collection | DOAJ |
| description | Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR) = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies. |
| format | Article |
| id | doaj-art-56bb7be103094e20a1ebafe269f259c2 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2014-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-56bb7be103094e20a1ebafe269f259c22025-08-20T02:22:45ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-08-01108e100451710.1371/journal.pgen.1004517Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.Maggie C Y NgDaniel ShrinerBrian H ChenJiang LiWei-Min ChenXiuqing GuoJiankang LiuSuzette J BielinskiLisa R YanekMichael A NallsMary E ComeauLaura J Rasmussen-TorvikRichard A JensenDaniel S EvansYan V SunPing AnSanjay R PatelYingchang LuJirong LongLoren L ArmstrongLynne WagenknechtLingyao YangBeverly M SnivelyNicholette D PalmerPoorva MudgalCarl D LangefeldKeith L KeeneBarry I FreedmanJosyf C MychaleckyjUma NayakLeslie J RaffelMark O GoodarziY-D Ida ChenHerman A TaylorAdolfo CorreaMario SimsDavid CouperJames S PankowEric BoerwinkleAdebowale AdeyemoAyo DoumateyGuanjie ChenRasika A MathiasDhananjay VaidyaAndrew B SingletonAlan B ZondermanRobert P IgoJohn R SedorFIND ConsortiumEdmond K KabagambeDavid S SiscovickBarbara McKnightKenneth RiceYongmei LiuWen-Chi HsuehWei ZhaoLawrence F BielakAldi KrajaMichael A ProvinceErwin P BottingerOmri GottesmanQiuyin CaiWei ZhengWilliam J BlotWilliam L LoweJennifer A PachecoDana C CrawfordeMERGE ConsortiumDIAGRAM ConsortiumElin GrundbergMuTHER ConsortiumStephen S RichM Geoffrey HayesXiao-Ou ShuRuth J F LoosIngrid B BoreckiPatricia A PeyserSteven R CummingsBruce M PsatyMyriam FornageSudha K IyengarMichele K EvansDiane M BeckerW H Linda KaoJames G WilsonJerome I RotterMichèle M SaleSimin LiuCharles N RotimiDonald W BowdenMEta-analysis of type 2 DIabetes in African Americans ConsortiumType 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR) = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.https://doi.org/10.1371/journal.pgen.1004517 |
| spellingShingle | Maggie C Y Ng Daniel Shriner Brian H Chen Jiang Li Wei-Min Chen Xiuqing Guo Jiankang Liu Suzette J Bielinski Lisa R Yanek Michael A Nalls Mary E Comeau Laura J Rasmussen-Torvik Richard A Jensen Daniel S Evans Yan V Sun Ping An Sanjay R Patel Yingchang Lu Jirong Long Loren L Armstrong Lynne Wagenknecht Lingyao Yang Beverly M Snively Nicholette D Palmer Poorva Mudgal Carl D Langefeld Keith L Keene Barry I Freedman Josyf C Mychaleckyj Uma Nayak Leslie J Raffel Mark O Goodarzi Y-D Ida Chen Herman A Taylor Adolfo Correa Mario Sims David Couper James S Pankow Eric Boerwinkle Adebowale Adeyemo Ayo Doumatey Guanjie Chen Rasika A Mathias Dhananjay Vaidya Andrew B Singleton Alan B Zonderman Robert P Igo John R Sedor FIND Consortium Edmond K Kabagambe David S Siscovick Barbara McKnight Kenneth Rice Yongmei Liu Wen-Chi Hsueh Wei Zhao Lawrence F Bielak Aldi Kraja Michael A Province Erwin P Bottinger Omri Gottesman Qiuyin Cai Wei Zheng William J Blot William L Lowe Jennifer A Pacheco Dana C Crawford eMERGE Consortium DIAGRAM Consortium Elin Grundberg MuTHER Consortium Stephen S Rich M Geoffrey Hayes Xiao-Ou Shu Ruth J F Loos Ingrid B Borecki Patricia A Peyser Steven R Cummings Bruce M Psaty Myriam Fornage Sudha K Iyengar Michele K Evans Diane M Becker W H Linda Kao James G Wilson Jerome I Rotter Michèle M Sale Simin Liu Charles N Rotimi Donald W Bowden MEta-analysis of type 2 DIabetes in African Americans Consortium Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. PLoS Genetics |
| title | Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. |
| title_full | Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. |
| title_fullStr | Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. |
| title_full_unstemmed | Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. |
| title_short | Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. |
| title_sort | meta analysis of genome wide association studies in african americans provides insights into the genetic architecture of type 2 diabetes |
| url | https://doi.org/10.1371/journal.pgen.1004517 |
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