Standard
An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans. / Scott, Robert A; Scott, Laura J; Mägi, Reedik; Marullo, Letizia; Gaulton, Kyle J; Kaakinen, Marika; Pervjakova, Natalia; Pers, Tune H; Johnson, Andrew D; Eicher, John D; Jackson, Anne U; Ferreira, Teresa; Lee, Yeji; Ma, Clement; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Qi, Lu; Van Zuydam, Natalie R; Mahajan, Anubha; Chen, Han; Almgren, Peter; Voight, Ben F; Grallert, Harald; Müller-Nurasyid, Martina; Ried, Janina S; Rayner, William N; Robertson, Neil; Karssen, Lennart C; van Leeuwen, Elisabeth M; Willems, Sara M; Fuchsberger, Christian; Kwan, Phoenix; Teslovich, Tanya M; Chanda, Pritam; Li, Man; Lu, Yingchang; Dina, Christian; Thuillier, Dorothee; Yengo, Loic; Jiang, Longda; Sparso, Thomas; Kestler, Hans A; Chheda, Himanshu; Eisele, Lewin; Gustafsson, Stefan; Frånberg, Mattias; Strawbridge, Rona J; Benediktsson, Rafn; Hreidarsson, Astradur B; Kong, Augustine; Sigurðsson, Gunnar; Kerrison, Nicola D; Luan, Jian'an; Liang, Liming; Meitinger, Thomas; Roden, Michael; Thorand, Barbara; Esko, Tõnu; Mihailov, Evelin; Fox, Caroline; Liu, Ching-Ti; Rybin, Denis; Isomaa, Bo; Lyssenko, Valeriya; Tuomi, Tiinamaija; Couper, David J; Pankow, James S; Grarup, Niels; Have, Christian T; Jørgensen, Marit E; Jørgensen, Torben; Linneberg, Allan; Cornelis, Marilyn C; van Dam, Rob M; Hunter, David J; Kraft, Peter; Sun, Qi; Edkins, Sarah; Owen, Katharine R; Perry, John Rb; Wood, Andrew R; Zeggini, Eleftheria; Tajes-Fernandes, Juan; Abecasis, Goncalo R; Bonnycastle, Lori L; Chines, Peter S; Stringham, Heather M; Koistinen, Heikki A; Kinnunen, Leena; Sennblad, Bengt; Mühleisen, Thomas W; Nöthen, Markus M; Pechlivanis, Sonali; Baldassarre, Damiano; Gertow, Karl; Humphries, Steve E; Tremoli, Elena; Klopp, Norman; Meyer, Julia; Steinbach, Gerald; Wennauer, Roman; Eriksson, Johan G; Mӓnnistö, Satu; Peltonen, Leena; Tikkanen, Emmi; Charpentier, Guillaume; Eury, Elodie; Lobbens, Stéphane; Gigante, Bruna; Leander, Karin; McLeod, Olga; Bottinger, Erwin P; Gottesman, Omri; Ruderfer, Douglas; Blüher, Matthias; Kovacs, Peter; Tonjes, Anke; Maruthur, Nisa M; Scapoli, Chiara; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; de Faire, Ulf; Hamsten, Anders; Stumvoll, Michael; Deloukas, Panagiotis; Donnelly, Peter J; Frayling, Timothy M; Hattersley, Andrew T; Ripatti, Samuli; Salomaa, Veikko; Pedersen, Nancy L; Boehm, Bernhard O; Bergman, Richard N; Collins, Francis S; Mohlke, Karen L; Tuomilehto, Jaakko; Hansen, Torben; Pedersen, Oluf; Barroso, Inês; Lannfelt, Lars; Ingelsson, Erik; Lind, Lars; Lindgren, Cecilia M; Cauchi, Stephane; Froguel, Philippe; Loos, Ruth Jf; Balkau, Beverley; Boeing, Heiner; Franks, Paul W; Gurrea, Aurelio Barricarte; Palli, Domenico; van der Schouw, Yvonne T; Altshuler, David; Groop, Leif C; Langenberg, Claudia; Wareham, Nicholas J; Sijbrands, Eric; van Duijn, Cornelia M; Florez, Jose C; Meigs, James B; Boerwinkle, Eric; Gieger, Christian; Strauch, Konstantin; Metspalu, Andres; Morris, Andrew D; Palmer, Colin Na; Hu, Frank B; Thorsteinsdottir, Unnur; Stefansson, Kari; Dupuis, Josée; Morris, Andrew P; Boehnke, Michael; McCarthy, Mark I; Prokopenko, Inga.
In:
Diabetes, Vol. 66, No. 11, 2017, p. 2888-2902.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Scott, RA, Scott, LJ, Mägi, R, Marullo, L, Gaulton, KJ, Kaakinen, M, Pervjakova, N
, Pers, TH, Johnson, AD, Eicher, JD, Jackson, AU, Ferreira, T, Lee, Y, Ma, C, Steinthorsdottir, V, Thorleifsson, G, Qi, L, Van Zuydam, NR, Mahajan, A, Chen, H, Almgren, P, Voight, BF, Grallert, H, Müller-Nurasyid, M, Ried, JS, Rayner, WN, Robertson, N, Karssen, LC, van Leeuwen, EM, Willems, SM, Fuchsberger, C, Kwan, P, Teslovich, TM, Chanda, P, Li, M, Lu, Y, Dina, C, Thuillier, D, Yengo, L, Jiang, L, Sparso, T, Kestler, HA, Chheda, H, Eisele, L, Gustafsson, S, Frånberg, M, Strawbridge, RJ, Benediktsson, R, Hreidarsson, AB, Kong, A, Sigurðsson, G, Kerrison, ND, Luan, J, Liang, L, Meitinger, T, Roden, M, Thorand, B, Esko, T, Mihailov, E, Fox, C, Liu, C-T, Rybin, D, Isomaa, B, Lyssenko, V, Tuomi, T, Couper, DJ, Pankow, JS
, Grarup, N, Have, CT, Jørgensen, ME, Jørgensen, T
, Linneberg, A, Cornelis, MC, van Dam, RM, Hunter, DJ, Kraft, P, Sun, Q, Edkins, S, Owen, KR, Perry, JR, Wood, AR, Zeggini, E, Tajes-Fernandes, J, Abecasis, GR, Bonnycastle, LL, Chines, PS, Stringham, HM, Koistinen, HA, Kinnunen, L, Sennblad, B, Mühleisen, TW, Nöthen, MM, Pechlivanis, S, Baldassarre, D, Gertow, K, Humphries, SE, Tremoli, E, Klopp, N, Meyer, J, Steinbach, G, Wennauer, R, Eriksson, JG, Mӓnnistö, S, Peltonen, L, Tikkanen, E, Charpentier, G, Eury, E, Lobbens, S, Gigante, B, Leander, K, McLeod, O, Bottinger, EP, Gottesman, O, Ruderfer, D, Blüher, M, Kovacs, P, Tonjes, A, Maruthur, NM, Scapoli, C, Erbel, R, Jöckel, K-H, Moebus, S, de Faire, U, Hamsten, A, Stumvoll, M, Deloukas, P, Donnelly, PJ, Frayling, TM, Hattersley, AT, Ripatti, S, Salomaa, V, Pedersen, NL, Boehm, BO, Bergman, RN, Collins, FS, Mohlke, KL, Tuomilehto, J
, Hansen, T, Pedersen, O, Barroso, I, Lannfelt, L, Ingelsson, E, Lind, L, Lindgren, CM, Cauchi, S, Froguel, P, Loos, RJ, Balkau, B, Boeing, H, Franks, PW, Gurrea, AB, Palli, D, van der Schouw, YT, Altshuler, D, Groop, LC, Langenberg, C, Wareham, NJ, Sijbrands, E, van Duijn, CM, Florez, JC, Meigs, JB, Boerwinkle, E, Gieger, C, Strauch, K, Metspalu, A, Morris, AD, Palmer, CN, Hu, FB, Thorsteinsdottir, U, Stefansson, K, Dupuis, J, Morris, AP, Boehnke, M, McCarthy, MI & Prokopenko, I 2017, '
An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans',
Diabetes, vol. 66, no. 11, pp. 2888-2902.
https://doi.org/10.2337/db16-1253APA
Scott, R. A., Scott, L. J., Mägi, R., Marullo, L., Gaulton, K. J., Kaakinen, M., Pervjakova, N.
, Pers, T. H., Johnson, A. D., Eicher, J. D., Jackson, A. U., Ferreira, T., Lee, Y., Ma, C., Steinthorsdottir, V., Thorleifsson, G., Qi, L., Van Zuydam, N. R., Mahajan, A., ... Prokopenko, I. (2017).
An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans.
Diabetes,
66(11), 2888-2902.
https://doi.org/10.2337/db16-1253Vancouver
Scott RA, Scott LJ, Mägi R, Marullo L, Gaulton KJ, Kaakinen M et al.
An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans.
Diabetes. 2017;66(11):2888-2902.
https://doi.org/10.2337/db16-1253Author
Scott, Robert A ; Scott, Laura J ; Mägi, Reedik ; Marullo, Letizia ; Gaulton, Kyle J ; Kaakinen, Marika ; Pervjakova, Natalia ; Pers, Tune H ; Johnson, Andrew D ; Eicher, John D ; Jackson, Anne U ; Ferreira, Teresa ; Lee, Yeji ; Ma, Clement ; Steinthorsdottir, Valgerdur ; Thorleifsson, Gudmar ; Qi, Lu ; Van Zuydam, Natalie R ; Mahajan, Anubha ; Chen, Han ; Almgren, Peter ; Voight, Ben F ; Grallert, Harald ; Müller-Nurasyid, Martina ; Ried, Janina S ; Rayner, William N ; Robertson, Neil ; Karssen, Lennart C ; van Leeuwen, Elisabeth M ; Willems, Sara M ; Fuchsberger, Christian ; Kwan, Phoenix ; Teslovich, Tanya M ; Chanda, Pritam ; Li, Man ; Lu, Yingchang ; Dina, Christian ; Thuillier, Dorothee ; Yengo, Loic ; Jiang, Longda ; Sparso, Thomas ; Kestler, Hans A ; Chheda, Himanshu ; Eisele, Lewin ; Gustafsson, Stefan ; Frånberg, Mattias ; Strawbridge, Rona J ; Benediktsson, Rafn ; Hreidarsson, Astradur B ; Kong, Augustine ; Sigurðsson, Gunnar ; Kerrison, Nicola D ; Luan, Jian'an ; Liang, Liming ; Meitinger, Thomas ; Roden, Michael ; Thorand, Barbara ; Esko, Tõnu ; Mihailov, Evelin ; Fox, Caroline ; Liu, Ching-Ti ; Rybin, Denis ; Isomaa, Bo ; Lyssenko, Valeriya ; Tuomi, Tiinamaija ; Couper, David J ; Pankow, James S ; Grarup, Niels ; Have, Christian T ; Jørgensen, Marit E ; Jørgensen, Torben ; Linneberg, Allan ; Cornelis, Marilyn C ; van Dam, Rob M ; Hunter, David J ; Kraft, Peter ; Sun, Qi ; Edkins, Sarah ; Owen, Katharine R ; Perry, John Rb ; Wood, Andrew R ; Zeggini, Eleftheria ; Tajes-Fernandes, Juan ; Abecasis, Goncalo R ; Bonnycastle, Lori L ; Chines, Peter S ; Stringham, Heather M ; Koistinen, Heikki A ; Kinnunen, Leena ; Sennblad, Bengt ; Mühleisen, Thomas W ; Nöthen, Markus M ; Pechlivanis, Sonali ; Baldassarre, Damiano ; Gertow, Karl ; Humphries, Steve E ; Tremoli, Elena ; Klopp, Norman ; Meyer, Julia ; Steinbach, Gerald ; Wennauer, Roman ; Eriksson, Johan G ; Mӓnnistö, Satu ; Peltonen, Leena ; Tikkanen, Emmi ; Charpentier, Guillaume ; Eury, Elodie ; Lobbens, Stéphane ; Gigante, Bruna ; Leander, Karin ; McLeod, Olga ; Bottinger, Erwin P ; Gottesman, Omri ; Ruderfer, Douglas ; Blüher, Matthias ; Kovacs, Peter ; Tonjes, Anke ; Maruthur, Nisa M ; Scapoli, Chiara ; Erbel, Raimund ; Jöckel, Karl-Heinz ; Moebus, Susanne ; de Faire, Ulf ; Hamsten, Anders ; Stumvoll, Michael ; Deloukas, Panagiotis ; Donnelly, Peter J ; Frayling, Timothy M ; Hattersley, Andrew T ; Ripatti, Samuli ; Salomaa, Veikko ; Pedersen, Nancy L ; Boehm, Bernhard O ; Bergman, Richard N ; Collins, Francis S ; Mohlke, Karen L ; Tuomilehto, Jaakko ; Hansen, Torben ; Pedersen, Oluf ; Barroso, Inês ; Lannfelt, Lars ; Ingelsson, Erik ; Lind, Lars ; Lindgren, Cecilia M ; Cauchi, Stephane ; Froguel, Philippe ; Loos, Ruth Jf ; Balkau, Beverley ; Boeing, Heiner ; Franks, Paul W ; Gurrea, Aurelio Barricarte ; Palli, Domenico ; van der Schouw, Yvonne T ; Altshuler, David ; Groop, Leif C ; Langenberg, Claudia ; Wareham, Nicholas J ; Sijbrands, Eric ; van Duijn, Cornelia M ; Florez, Jose C ; Meigs, James B ; Boerwinkle, Eric ; Gieger, Christian ; Strauch, Konstantin ; Metspalu, Andres ; Morris, Andrew D ; Palmer, Colin Na ; Hu, Frank B ; Thorsteinsdottir, Unnur ; Stefansson, Kari ; Dupuis, Josée ; Morris, Andrew P ; Boehnke, Michael ; McCarthy, Mark I ; Prokopenko, Inga. / An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans. In: Diabetes. 2017 ; Vol. 66, No. 11. pp. 2888-2902.
Bibtex
@article{186f98569b4a4825b7dd9300b4c708b2,
title = "An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans",
abstract = "To characterise type 2 diabetes (T2D) associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D cases and 132,532 controls of European ancestry after imputation using the 1000 Genomes multi-ethnic reference panel. Promising association signals were followed-up in additional data sets (of 14,545 or 7,397 T2D cases and 38,994 or 71,604 controls). We identified 13 novel T2D-associated loci (p<5×10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common SNVs. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion, and in adipocytes, monocytes and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.",
keywords = "Journal Article",
author = "Scott, {Robert A} and Scott, {Laura J} and Reedik M{\"a}gi and Letizia Marullo and Gaulton, {Kyle J} and Marika Kaakinen and Natalia Pervjakova and Pers, {Tune H} and Johnson, {Andrew D} and Eicher, {John D} and Jackson, {Anne U} and Teresa Ferreira and Yeji Lee and Clement Ma and Valgerdur Steinthorsdottir and Gudmar Thorleifsson and Lu Qi and {Van Zuydam}, {Natalie R} and Anubha Mahajan and Han Chen and Peter Almgren and Voight, {Ben F} and Harald Grallert and Martina M{\"u}ller-Nurasyid and Ried, {Janina S} and Rayner, {William N} and Neil Robertson and Karssen, {Lennart C} and {van Leeuwen}, {Elisabeth M} and Willems, {Sara M} and Christian Fuchsberger and Phoenix Kwan and Teslovich, {Tanya M} and Pritam Chanda and Man Li and Yingchang Lu and Christian Dina and Dorothee Thuillier and Loic Yengo and Longda Jiang and Thomas Sparso and Kestler, {Hans A} and Himanshu Chheda and Lewin Eisele and Stefan Gustafsson and Mattias Fr{\aa}nberg and Strawbridge, {Rona J} and Rafn Benediktsson and Hreidarsson, {Astradur B} and Augustine Kong and Gunnar Sigur{\dh}sson and Kerrison, {Nicola D} and Jian'an Luan and Liming Liang and Thomas Meitinger and Michael Roden and Barbara Thorand and T{\~o}nu Esko and Evelin Mihailov and Caroline Fox and Ching-Ti Liu and Denis Rybin and Bo Isomaa and Valeriya Lyssenko and Tiinamaija Tuomi and Couper, {David J} and Pankow, {James S} and Niels Grarup and Have, {Christian T} and J{\o}rgensen, {Marit E} and Torben J{\o}rgensen and Allan Linneberg and Cornelis, {Marilyn C} and {van Dam}, {Rob M} and Hunter, {David J} and Peter Kraft and Qi Sun and Sarah Edkins and Owen, {Katharine R} and Perry, {John Rb} and Wood, {Andrew R} and Eleftheria Zeggini and Juan Tajes-Fernandes and Abecasis, {Goncalo R} and Bonnycastle, {Lori L} and Chines, {Peter S} and Stringham, {Heather M} and Koistinen, {Heikki A} and Leena Kinnunen and Bengt Sennblad and M{\"u}hleisen, {Thomas W} and N{\"o}then, {Markus M} and Sonali Pechlivanis and Damiano Baldassarre and Karl Gertow and Humphries, {Steve E} and Elena Tremoli and Norman Klopp and Julia Meyer and Gerald Steinbach and Roman Wennauer and Eriksson, {Johan G} and Satu Mӓnnist{\"o} and Leena Peltonen and Emmi Tikkanen and Guillaume Charpentier and Elodie Eury and St{\'e}phane Lobbens and Bruna Gigante and Karin Leander and Olga McLeod and Bottinger, {Erwin P} and Omri Gottesman and Douglas Ruderfer and Matthias Bl{\"u}her and Peter Kovacs and Anke Tonjes and Maruthur, {Nisa M} and Chiara Scapoli and Raimund Erbel and Karl-Heinz J{\"o}ckel and Susanne Moebus and {de Faire}, Ulf and Anders Hamsten and Michael Stumvoll and Panagiotis Deloukas and Donnelly, {Peter J} and Frayling, {Timothy M} and Hattersley, {Andrew T} and Samuli Ripatti and Veikko Salomaa and Pedersen, {Nancy L} and Boehm, {Bernhard O} and Bergman, {Richard N} and Collins, {Francis S} and Mohlke, {Karen L} and Jaakko Tuomilehto and Torben Hansen and Oluf Pedersen and In{\^e}s Barroso and Lars Lannfelt and Erik Ingelsson and Lars Lind and Lindgren, {Cecilia M} and Stephane Cauchi and Philippe Froguel and Loos, {Ruth Jf} and Beverley Balkau and Heiner Boeing and Franks, {Paul W} and Gurrea, {Aurelio Barricarte} and Domenico Palli and {van der Schouw}, {Yvonne T} and David Altshuler and Groop, {Leif C} and Claudia Langenberg and Wareham, {Nicholas J} and Eric Sijbrands and {van Duijn}, {Cornelia M} and Florez, {Jose C} and Meigs, {James B} and Eric Boerwinkle and Christian Gieger and Konstantin Strauch and Andres Metspalu and Morris, {Andrew D} and Palmer, {Colin Na} and Hu, {Frank B} and Unnur Thorsteinsdottir and Kari Stefansson and Jos{\'e}e Dupuis and Morris, {Andrew P} and Michael Boehnke and McCarthy, {Mark I} and Inga Prokopenko",
note = "{\textcopyright} 2017 by the American Diabetes Association.",
year = "2017",
doi = "10.2337/db16-1253",
language = "English",
volume = "66",
pages = "2888--2902",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "11",
}
RIS
TY - JOUR
T1 - An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
AU - Scott, Robert A
AU - Scott, Laura J
AU - Mägi, Reedik
AU - Marullo, Letizia
AU - Gaulton, Kyle J
AU - Kaakinen, Marika
AU - Pervjakova, Natalia
AU - Pers, Tune H
AU - Johnson, Andrew D
AU - Eicher, John D
AU - Jackson, Anne U
AU - Ferreira, Teresa
AU - Lee, Yeji
AU - Ma, Clement
AU - Steinthorsdottir, Valgerdur
AU - Thorleifsson, Gudmar
AU - Qi, Lu
AU - Van Zuydam, Natalie R
AU - Mahajan, Anubha
AU - Chen, Han
AU - Almgren, Peter
AU - Voight, Ben F
AU - Grallert, Harald
AU - Müller-Nurasyid, Martina
AU - Ried, Janina S
AU - Rayner, William N
AU - Robertson, Neil
AU - Karssen, Lennart C
AU - van Leeuwen, Elisabeth M
AU - Willems, Sara M
AU - Fuchsberger, Christian
AU - Kwan, Phoenix
AU - Teslovich, Tanya M
AU - Chanda, Pritam
AU - Li, Man
AU - Lu, Yingchang
AU - Dina, Christian
AU - Thuillier, Dorothee
AU - Yengo, Loic
AU - Jiang, Longda
AU - Sparso, Thomas
AU - Kestler, Hans A
AU - Chheda, Himanshu
AU - Eisele, Lewin
AU - Gustafsson, Stefan
AU - Frånberg, Mattias
AU - Strawbridge, Rona J
AU - Benediktsson, Rafn
AU - Hreidarsson, Astradur B
AU - Kong, Augustine
AU - Sigurðsson, Gunnar
AU - Kerrison, Nicola D
AU - Luan, Jian'an
AU - Liang, Liming
AU - Meitinger, Thomas
AU - Roden, Michael
AU - Thorand, Barbara
AU - Esko, Tõnu
AU - Mihailov, Evelin
AU - Fox, Caroline
AU - Liu, Ching-Ti
AU - Rybin, Denis
AU - Isomaa, Bo
AU - Lyssenko, Valeriya
AU - Tuomi, Tiinamaija
AU - Couper, David J
AU - Pankow, James S
AU - Grarup, Niels
AU - Have, Christian T
AU - Jørgensen, Marit E
AU - Jørgensen, Torben
AU - Linneberg, Allan
AU - Cornelis, Marilyn C
AU - van Dam, Rob M
AU - Hunter, David J
AU - Kraft, Peter
AU - Sun, Qi
AU - Edkins, Sarah
AU - Owen, Katharine R
AU - Perry, John Rb
AU - Wood, Andrew R
AU - Zeggini, Eleftheria
AU - Tajes-Fernandes, Juan
AU - Abecasis, Goncalo R
AU - Bonnycastle, Lori L
AU - Chines, Peter S
AU - Stringham, Heather M
AU - Koistinen, Heikki A
AU - Kinnunen, Leena
AU - Sennblad, Bengt
AU - Mühleisen, Thomas W
AU - Nöthen, Markus M
AU - Pechlivanis, Sonali
AU - Baldassarre, Damiano
AU - Gertow, Karl
AU - Humphries, Steve E
AU - Tremoli, Elena
AU - Klopp, Norman
AU - Meyer, Julia
AU - Steinbach, Gerald
AU - Wennauer, Roman
AU - Eriksson, Johan G
AU - Mӓnnistö, Satu
AU - Peltonen, Leena
AU - Tikkanen, Emmi
AU - Charpentier, Guillaume
AU - Eury, Elodie
AU - Lobbens, Stéphane
AU - Gigante, Bruna
AU - Leander, Karin
AU - McLeod, Olga
AU - Bottinger, Erwin P
AU - Gottesman, Omri
AU - Ruderfer, Douglas
AU - Blüher, Matthias
AU - Kovacs, Peter
AU - Tonjes, Anke
AU - Maruthur, Nisa M
AU - Scapoli, Chiara
AU - Erbel, Raimund
AU - Jöckel, Karl-Heinz
AU - Moebus, Susanne
AU - de Faire, Ulf
AU - Hamsten, Anders
AU - Stumvoll, Michael
AU - Deloukas, Panagiotis
AU - Donnelly, Peter J
AU - Frayling, Timothy M
AU - Hattersley, Andrew T
AU - Ripatti, Samuli
AU - Salomaa, Veikko
AU - Pedersen, Nancy L
AU - Boehm, Bernhard O
AU - Bergman, Richard N
AU - Collins, Francis S
AU - Mohlke, Karen L
AU - Tuomilehto, Jaakko
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - Barroso, Inês
AU - Lannfelt, Lars
AU - Ingelsson, Erik
AU - Lind, Lars
AU - Lindgren, Cecilia M
AU - Cauchi, Stephane
AU - Froguel, Philippe
AU - Loos, Ruth Jf
AU - Balkau, Beverley
AU - Boeing, Heiner
AU - Franks, Paul W
AU - Gurrea, Aurelio Barricarte
AU - Palli, Domenico
AU - van der Schouw, Yvonne T
AU - Altshuler, David
AU - Groop, Leif C
AU - Langenberg, Claudia
AU - Wareham, Nicholas J
AU - Sijbrands, Eric
AU - van Duijn, Cornelia M
AU - Florez, Jose C
AU - Meigs, James B
AU - Boerwinkle, Eric
AU - Gieger, Christian
AU - Strauch, Konstantin
AU - Metspalu, Andres
AU - Morris, Andrew D
AU - Palmer, Colin Na
AU - Hu, Frank B
AU - Thorsteinsdottir, Unnur
AU - Stefansson, Kari
AU - Dupuis, Josée
AU - Morris, Andrew P
AU - Boehnke, Michael
AU - McCarthy, Mark I
AU - Prokopenko, Inga
N1 - © 2017 by the American Diabetes Association.
PY - 2017
Y1 - 2017
N2 - To characterise type 2 diabetes (T2D) associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D cases and 132,532 controls of European ancestry after imputation using the 1000 Genomes multi-ethnic reference panel. Promising association signals were followed-up in additional data sets (of 14,545 or 7,397 T2D cases and 38,994 or 71,604 controls). We identified 13 novel T2D-associated loci (p<5×10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common SNVs. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion, and in adipocytes, monocytes and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
AB - To characterise type 2 diabetes (T2D) associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D cases and 132,532 controls of European ancestry after imputation using the 1000 Genomes multi-ethnic reference panel. Promising association signals were followed-up in additional data sets (of 14,545 or 7,397 T2D cases and 38,994 or 71,604 controls). We identified 13 novel T2D-associated loci (p<5×10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common SNVs. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion, and in adipocytes, monocytes and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
KW - Journal Article
U2 - 10.2337/db16-1253
DO - 10.2337/db16-1253
M3 - Journal article
C2 - 28566273
VL - 66
SP - 2888
EP - 2902
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 11
ER -
