Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

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Ng, Maggie C. Y.; Shriner, Daniel; Chen, Brian H.; Li, Jiang; Chen, Wei-Min; Guo, Xiuqing; Liu, Jiankang; Bielinski, Suzette J.; Yanek, Lisa R.; Nalls, Michael A.; Comeau, Mary E.; Rasmussen-Torvik, Laura J.; Jensen, Richard A.; Evans, Daniel S.; Sun, Yan V.; An, Ping; Patel, Sanjay R.; Lu, Yingchang; Long, Jirong; Armstrong, Loren L.; Wagenknecht, Lynne; Yang, Lingyao; Snively, Beverly M.; Palmer, Nicholette D.; Mudgal, Poorva; Langefeld, Carl D.; Keene, Keith L.; Freedman, Barry I.; Mychaleckyj, Josyf C.; Nayak, Uma; Raffel, Leslie J.; Goodarzi, Mark O.; Chen, Y-D Ida; Taylor, Herman A.; Correa, Adolfo; Sims, Mario; Couper, David J.; Pankow, James S.; Boerwinkle, Eric; Adeyemo, Adebowale; Doumatey, Ayo; Chen, Guanjie; Mathias, Rasika A.; Vaidya, Dhananjay; Singleton, Andrew B.; Zonderman, Alan B.; Igo, Robert P.; Sedor, John R.; Kabagambe, Edmond K.; Siscovick, David S.; McKnight, Barbara; Rice, Kenneth; Liu, Yongmei; Hsueh, Wen-Chi; Zhao, Wei; Bielak, Lawrence F.; Kraja, Aldi; Province, Michael A.; Bottinger, Erwin P.; Gottesman, Omri; Cai, Qiuyin; Zheng, Wei; Blot, William J.; Lowe, William L.; Pacheco, Jennifer A.; Crawford, Dana C.; Grundberg, Elin; Rich, Stephen S.; Hayes, M. Geoffrey; Shu, Xiao-Ou; Loos, Ruth J. F.; Borecki, Ingrid B.; Peyser, Patricia A.; Cummings, Steven R.; Psaty, Bruce M.; Fornage, Myriam; Iyengar, Sudha K.; Evans, Michele K.; Becker, Diane M.; Kao, W. H. Linda; Wilson, James G.; Rotter, Jerome I.; Sale, Michèle M.; Liu, Simin; Rotimi, Charles N.; Bowden, Donald W.
Abstract
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.
URI
http://hdl.handle.net/10342/5472
Subject
 African Americans; Meta-analysis; Genetic loci; Homeostasis; Diabetes mellitus; Variant genotypes; Glucose 
Date
2014-08
Citation:
APA:
Ng, Maggie C. Y., & Shriner, Daniel, & Chen, Brian H., & Li, Jiang, & Chen, Wei-Min, & Guo, Xiuqing, & Liu, Jiankang, & Bielinski, Suzette J., & Yanek, Lisa R., & Nalls, Michael A., & Comeau, Mary E., & Rasmussen-Torvik, Laura J., & Jensen, Richard A., & Evans, Daniel S., & Sun, Yan V., & An, Ping, & Patel, Sanjay R., & Lu, Yingchang, & Long, Jirong, & Armstrong, Loren L., & Wagenknecht, Lynne, & Yang, Lingyao, & Snively, Beverly M., & Palmer, Nicholette D., & Mudgal, Poorva, & Langefeld, Carl D., & Keene, Keith L., & Freedman, Barry I., & Mychaleckyj, Josyf C., & Nayak, Uma, & Raffel, Leslie J., & Goodarzi, Mark O., & Chen, Y-D Ida, & Taylor, Herman A., & Correa, Adolfo, & Sims, Mario, & Couper, David J., & Pankow, James S., & Boerwinkle, Eric, & Adeyemo, Adebowale, & Doumatey, Ayo, & Chen, Guanjie, & Mathias, Rasika A., & Vaidya, Dhananjay, & Singleton, Andrew B., & Zonderman, Alan B., & Igo, Robert P., & Sedor, John R., & Kabagambe, Edmond K., & Siscovick, David S., & McKnight, Barbara, & Rice, Kenneth, & Liu, Yongmei, & Hsueh, Wen-Chi, & Zhao, Wei, & Bielak, Lawrence F., & Kraja, Aldi, & Province, Michael A., & Bottinger, Erwin P., & Gottesman, Omri, & Cai, Qiuyin, & Zheng, Wei, & Blot, William J., & Lowe, William L., & Pacheco, Jennifer A., & Crawford, Dana C., & Grundberg, Elin, & Rich, Stephen S., & Hayes, M. Geoffrey, & Shu, Xiao-Ou, & Loos, Ruth J. F., & Borecki, Ingrid B., & Peyser, Patricia A., & Cummings, Steven R., & Psaty, Bruce M., & Fornage, Myriam, & Iyengar, Sudha K., & Evans, Michele K., & Becker, Diane M., & Kao, W. H. Linda, & Wilson, James G., & Rotter, Jerome I., & Sale, Michèle M., & Liu, Simin, & Rotimi, Charles N., & Bowden, Donald W.. (August 2014). Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes. PLoS Genetics, (10:8), p.1-14. Retrieved from http://hdl.handle.net/10342/5472

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MLA:
Ng, Maggie C. Y., and Shriner, Daniel, and Chen, Brian H., and Li, Jiang, and Chen, Wei-Min, and Guo, Xiuqing, and Liu, Jiankang, and Bielinski, Suzette J., and Yanek, Lisa R., and Nalls, Michael A., and Comeau, Mary E., and Rasmussen-Torvik, Laura J., and Jensen, Richard A., and Evans, Daniel S., and Sun, Yan V., and An, Ping, and Patel, Sanjay R., and Lu, Yingchang, and Long, Jirong, and Armstrong, Loren L., and Wagenknecht, Lynne, and Yang, Lingyao, and Snively, Beverly M., and Palmer, Nicholette D., and Mudgal, Poorva, and Langefeld, Carl D., and Keene, Keith L., and Freedman, Barry I., and Mychaleckyj, Josyf C., and Nayak, Uma, and Raffel, Leslie J., and Goodarzi, Mark O., and Chen, Y-D Ida, and Taylor, Herman A., and Correa, Adolfo, and Sims, Mario, and Couper, David J., and Pankow, James S., and Boerwinkle, Eric, and Adeyemo, Adebowale, and Doumatey, Ayo, and Chen, Guanjie, and Mathias, Rasika A., and Vaidya, Dhananjay, and Singleton, Andrew B., and Zonderman, Alan B., and Igo, Robert P., and Sedor, John R., and Kabagambe, Edmond K., and Siscovick, David S., and McKnight, Barbara, and Rice, Kenneth, and Liu, Yongmei, and Hsueh, Wen-Chi, and Zhao, Wei, and Bielak, Lawrence F., and Kraja, Aldi, and Province, Michael A., and Bottinger, Erwin P., and Gottesman, Omri, and Cai, Qiuyin, and Zheng, Wei, and Blot, William J., and Lowe, William L., and Pacheco, Jennifer A., and Crawford, Dana C., and Grundberg, Elin, and Rich, Stephen S., and Hayes, M. Geoffrey, and Shu, Xiao-Ou, and Loos, Ruth J. F., and Borecki, Ingrid B., and Peyser, Patricia A., and Cummings, Steven R., and Psaty, Bruce M., and Fornage, Myriam, and Iyengar, Sudha K., and Evans, Michele K., and Becker, Diane M., and Kao, W. H. Linda, and Wilson, James G., and Rotter, Jerome I., and Sale, Michèle M., and Liu, Simin, and Rotimi, Charles N., and Bowden, Donald W.. "Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes". PLoS Genetics. 10:8. (1-14.), August 2014. February 18, 2020. http://hdl.handle.net/10342/5472.
Chicago:
Ng, Maggie C. Y. and Shriner, Daniel and Chen, Brian H. and Li, Jiang and Chen, Wei-Min and Guo, Xiuqing and Liu, Jiankang and Bielinski, Suzette J. and Yanek, Lisa R. and Nalls, Michael A. and Comeau, Mary E. and Rasmussen-Torvik, Laura J. and Jensen, Richard A. and Evans, Daniel S. and Sun, Yan V. and An, Ping and Patel, Sanjay R. and Lu, Yingchang and Long, Jirong and Armstrong, Loren L. and Wagenknecht, Lynne and Yang, Lingyao and Snively, Beverly M. and Palmer, Nicholette D. and Mudgal, Poorva and Langefeld, Carl D. and Keene, Keith L. and Freedman, Barry I. and Mychaleckyj, Josyf C. and Nayak, Uma and Raffel, Leslie J. and Goodarzi, Mark O. and Chen, Y-D Ida and Taylor, Herman A. and Correa, Adolfo and Sims, Mario and Couper, David J. and Pankow, James S. and Boerwinkle, Eric and Adeyemo, Adebowale and Doumatey, Ayo and Chen, Guanjie and Mathias, Rasika A. and Vaidya, Dhananjay and Singleton, Andrew B. and Zonderman, Alan B. and Igo, Robert P. and Sedor, John R. and Kabagambe, Edmond K. and Siscovick, David S. and McKnight, Barbara and Rice, Kenneth and Liu, Yongmei and Hsueh, Wen-Chi and Zhao, Wei and Bielak, Lawrence F. and Kraja, Aldi and Province, Michael A. and Bottinger, Erwin P. and Gottesman, Omri and Cai, Qiuyin and Zheng, Wei and Blot, William J. and Lowe, William L. and Pacheco, Jennifer A. and Crawford, Dana C. and Grundberg, Elin and Rich, Stephen S. and Hayes, M. Geoffrey and Shu, Xiao-Ou and Loos, Ruth J. F. and Borecki, Ingrid B. and Peyser, Patricia A. and Cummings, Steven R. and Psaty, Bruce M. and Fornage, Myriam and Iyengar, Sudha K. and Evans, Michele K. and Becker, Diane M. and Kao, W. H. Linda and Wilson, James G. and Rotter, Jerome I. and Sale, Michèle M. and Liu, Simin and Rotimi, Charles N. and Bowden, Donald W., "Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes," PLoS Genetics 10, no. 8 (August 2014), http://hdl.handle.net/10342/5472 (accessed February 18, 2020).
AMA:
Ng, Maggie C. Y., Shriner, Daniel, Chen, Brian H., Li, Jiang, Chen, Wei-Min, Guo, Xiuqing, Liu, Jiankang, Bielinski, Suzette J., Yanek, Lisa R., Nalls, Michael A., Comeau, Mary E., Rasmussen-Torvik, Laura J., Jensen, Richard A., Evans, Daniel S., Sun, Yan V., An, Ping, Patel, Sanjay R., Lu, Yingchang, Long, Jirong, Armstrong, Loren L., Wagenknecht, Lynne, Yang, Lingyao, Snively, Beverly M., Palmer, Nicholette D., Mudgal, Poorva, Langefeld, Carl D., Keene, Keith L., Freedman, Barry I., Mychaleckyj, Josyf C., Nayak, Uma, Raffel, Leslie J., Goodarzi, Mark O., Chen, Y-D Ida, Taylor, Herman A., Correa, Adolfo, Sims, Mario, Couper, David J., Pankow, James S., Boerwinkle, Eric, Adeyemo, Adebowale, Doumatey, Ayo, Chen, Guanjie, Mathias, Rasika A., Vaidya, Dhananjay, Singleton, Andrew B., Zonderman, Alan B., Igo, Robert P., Sedor, John R., Kabagambe, Edmond K., Siscovick, David S., McKnight, Barbara, Rice, Kenneth, Liu, Yongmei, Hsueh, Wen-Chi, Zhao, Wei, Bielak, Lawrence F., Kraja, Aldi, Province, Michael A., Bottinger, Erwin P., Gottesman, Omri, Cai, Qiuyin, Zheng, Wei, Blot, William J., Lowe, William L., Pacheco, Jennifer A., Crawford, Dana C., Grundberg, Elin, Rich, Stephen S., Hayes, M. Geoffrey, Shu, Xiao-Ou, Loos, Ruth J. F., Borecki, Ingrid B., Peyser, Patricia A., Cummings, Steven R., Psaty, Bruce M., Fornage, Myriam, Iyengar, Sudha K., Evans, Michele K., Becker, Diane M., Kao, W. H. Linda, Wilson, James G., Rotter, Jerome I., Sale, Michèle M., Liu, Simin, Rotimi, Charles N., Bowden, Donald W.. Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes. PLoS Genetics. August 2014; 10(8) 1-14. http://hdl.handle.net/10342/5472. Accessed February 18, 2020.
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