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Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes

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Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. / 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; 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; FIND Consortium.

In: PLOS GENET, Vol. 10, No. 8, 08.2014, p. e1004517.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Ng, MCY, Shriner, D, Chen, BH, Li, J, Chen, W-M, Guo, X, Liu, J, Bielinski, SJ, Yanek, LR, Nalls, MA, Comeau, ME, Rasmussen-Torvik, LJ, Jensen, RA, Evans, DS, Sun, YV, An, P, Patel, SR, Lu, Y, Long, J, Armstrong, LL, Wagenknecht, L, Yang, L, Snively, BM, Palmer, ND, Mudgal, P, Langefeld, CD, Keene, KL, Freedman, BI, Mychaleckyj, JC, Nayak, U, Raffel, LJ, Goodarzi, MO, Chen, Y-DI, Taylor, HA, Correa, A, Sims, M, Couper, D, Pankow, JS, Boerwinkle, E, Adeyemo, A, Doumatey, A, Chen, G, Mathias, RA, Vaidya, D, Singleton, AB, Zonderman, AB, Igo, RP, Sedor, JR, Kabagambe, EK, Siscovick, DS, McKnight, B, Rice, K, Liu, Y, Hsueh, W-C, Zhao, W, Bielak, LF, Kraja, A, Province, MA, Bottinger, EP, Gottesman, O, Cai, Q, Zheng, W, Blot, WJ, Lowe, WL, Pacheco, JA, Crawford, DC, Grundberg, E, Rich, SS, Hayes, MG, Shu, X-O, Loos, RJF, Borecki, IB, Peyser, PA, Cummings, SR, Psaty, BM, Fornage, M, Iyengar, SK, Evans, MK, Becker, DM, Kao, WHL, Wilson, JG, Rotter, JI, Sale, MM, Liu, S, Rotimi, CN, Bowden, DW & FIND Consortium 2014, 'Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes', PLOS GENET, vol. 10, no. 8, pp. e1004517. https://doi.org/10.1371/journal.pgen.1004517

APA

Ng, M. C. Y., Shriner, D., Chen, B. H., Li, J., Chen, W-M., Guo, X., Liu, J., Bielinski, S. J., Yanek, L. R., Nalls, M. A., Comeau, M. E., Rasmussen-Torvik, L. J., Jensen, R. A., Evans, D. S., Sun, Y. V., An, P., Patel, S. R., Lu, Y., Long, J., ... FIND Consortium (2014). Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. PLOS GENET, 10(8), e1004517. https://doi.org/10.1371/journal.pgen.1004517

Vancouver

Ng MCY, Shriner D, Chen BH, Li J, Chen W-M, Guo X et al. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. PLOS GENET. 2014 Aug;10(8):e1004517. https://doi.org/10.1371/journal.pgen.1004517

Bibtex

@article{2af6dbad4f744a1aa19c3731eef750e7,
title = "Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes",
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.",
keywords = "African Americans, Diabetes Mellitus, Type 2, Genome-Wide Association Study, HLA-B27 Antigen, HMGA2 Protein, Humans, KCNQ1 Potassium Channel, Mutant Chimeric Proteins, Polymorphism, Single Nucleotide, Transcription Factor 7-Like 2 Protein, Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.",
author = "Ng, {Maggie C Y} and Daniel Shriner and Chen, {Brian H} and Jiang Li and Wei-Min Chen and Xiuqing Guo and Jiankang Liu 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 Ping An and Patel, {Sanjay R} and Yingchang Lu and Jirong Long and Armstrong, {Loren L} and Lynne Wagenknecht and Lingyao Yang and Snively, {Beverly M} and Palmer, {Nicholette D} and Poorva Mudgal and Langefeld, {Carl D} and Keene, {Keith L} and Freedman, {Barry I} and Mychaleckyj, {Josyf C} and Uma Nayak and Raffel, {Leslie J} and Goodarzi, {Mark O} and Chen, {Y-D Ida} and Taylor, {Herman A} and Adolfo Correa and Mario Sims and David Couper and Pankow, {James S} and Eric Boerwinkle and Adebowale Adeyemo and Ayo Doumatey and Guanjie Chen and Mathias, {Rasika A} and Dhananjay Vaidya 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 Barbara McKnight and Kenneth Rice and Yongmei Liu and Wen-Chi Hsueh and Wei Zhao and Bielak, {Lawrence F} and Aldi Kraja and Province, {Michael A} and Bottinger, {Erwin P} and Omri Gottesman and Qiuyin Cai and Wei Zheng and Blot, {William J} and Lowe, {William L} and Pacheco, {Jennifer A} and Crawford, {Dana C} and Elin Grundberg and Rich, {Stephen S} and Hayes, {M Geoffrey} and Xiao-Ou Shu and Loos, {Ruth J F} and Borecki, {Ingrid B} and Peyser, {Patricia A} and Cummings, {Steven R} and Psaty, {Bruce M} and Myriam Fornage 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, {Mich{\`e}le M} and Simin Liu and Rotimi, {Charles N} and Bowden, {Donald W} and {FIND Consortium} and Rosemarie Pl{\"a}tke",
year = "2014",
month = aug,
doi = "10.1371/journal.pgen.1004517",
language = "English",
volume = "10",
pages = "e1004517",
journal = "PLOS GENET",
issn = "1553-7404",
publisher = "Public Library of Science",
number = "8",

}

RIS

TY - JOUR

T1 - Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes

AU - Ng, Maggie C Y

AU - Shriner, Daniel

AU - Chen, Brian H

AU - Li, Jiang

AU - Chen, Wei-Min

AU - Guo, Xiuqing

AU - Liu, Jiankang

AU - Bielinski, Suzette J

AU - Yanek, Lisa R

AU - Nalls, Michael A

AU - Comeau, Mary E

AU - Rasmussen-Torvik, Laura J

AU - Jensen, Richard A

AU - Evans, Daniel S

AU - Sun, Yan V

AU - An, Ping

AU - Patel, Sanjay R

AU - Lu, Yingchang

AU - Long, Jirong

AU - Armstrong, Loren L

AU - Wagenknecht, Lynne

AU - Yang, Lingyao

AU - Snively, Beverly M

AU - Palmer, Nicholette D

AU - Mudgal, Poorva

AU - Langefeld, Carl D

AU - Keene, Keith L

AU - Freedman, Barry I

AU - Mychaleckyj, Josyf C

AU - Nayak, Uma

AU - Raffel, Leslie J

AU - Goodarzi, Mark O

AU - Chen, Y-D Ida

AU - Taylor, Herman A

AU - Correa, Adolfo

AU - Sims, Mario

AU - Couper, David

AU - Pankow, James S

AU - Boerwinkle, Eric

AU - Adeyemo, Adebowale

AU - Doumatey, Ayo

AU - Chen, Guanjie

AU - Mathias, Rasika A

AU - Vaidya, Dhananjay

AU - Singleton, Andrew B

AU - Zonderman, Alan B

AU - Igo, Robert P

AU - Sedor, John R

AU - Kabagambe, Edmond K

AU - Siscovick, David S

AU - McKnight, Barbara

AU - Rice, Kenneth

AU - Liu, Yongmei

AU - Hsueh, Wen-Chi

AU - Zhao, Wei

AU - Bielak, Lawrence F

AU - Kraja, Aldi

AU - Province, Michael A

AU - Bottinger, Erwin P

AU - Gottesman, Omri

AU - Cai, Qiuyin

AU - Zheng, Wei

AU - Blot, William J

AU - Lowe, William L

AU - Pacheco, Jennifer A

AU - Crawford, Dana C

AU - Grundberg, Elin

AU - Rich, Stephen S

AU - Hayes, M Geoffrey

AU - Shu, Xiao-Ou

AU - Loos, Ruth J F

AU - Borecki, Ingrid B

AU - Peyser, Patricia A

AU - Cummings, Steven R

AU - Psaty, Bruce M

AU - Fornage, Myriam

AU - Iyengar, Sudha K

AU - Evans, Michele K

AU - Becker, Diane M

AU - Kao, W H Linda

AU - Wilson, James G

AU - Rotter, Jerome I

AU - Sale, Michèle M

AU - Liu, Simin

AU - Rotimi, Charles N

AU - Bowden, Donald W

AU - FIND Consortium

AU - Plätke, Rosemarie

PY - 2014/8

Y1 - 2014/8

N2 - 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.

AB - 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.

KW - African Americans

KW - Diabetes Mellitus, Type 2

KW - Genome-Wide Association Study

KW - HLA-B27 Antigen

KW - HMGA2 Protein

KW - Humans

KW - KCNQ1 Potassium Channel

KW - Mutant Chimeric Proteins

KW - Polymorphism, Single Nucleotide

KW - Transcription Factor 7-Like 2 Protein

KW - Journal Article

KW - Meta-Analysis

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, Non-P.H.S.

KW - Research Support, U.S. Gov't, P.H.S.

U2 - 10.1371/journal.pgen.1004517

DO - 10.1371/journal.pgen.1004517

M3 - SCORING: Journal article

C2 - 25102180

VL - 10

SP - e1004517

JO - PLOS GENET

JF - PLOS GENET

SN - 1553-7404

IS - 8

ER -