An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans. 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., Chen, H., Almgren, P., Voight, B. F, Grallert, H., Müller-Nurasyid, M., Ried, J. S, Rayner, N. W, Robertson, N., Karssen, L. C, van Leeuwen, E. M, Willems, S. M, Fuchsberger, C., Kwan, P., Teslovich, T. M, Chanda, P., Li, M., Lu, Y., Dina, C., Thuillier, D., Yengo, L., Jiang, L., Sparso, T., Kestler, H. A, Chheda, H., Eisele, L., Gustafsson, S., Frånberg, M., Strawbridge, R. J, Benediktsson, R., Hreidarsson, A. B, Kong, A., Sigurðsson, G., Kerrison, N. D, Luan, J., Liang, L., Meitinger, T., Roden, M., Thorand, B., Esko, T., Mihailov, E., Fox, C., Liu, C., Rybin, D., Isomaa, B., Lyssenko, V., Tuomi, T., Couper, D. J, Pankow, J. S, Grarup, N., Have, C. T, Jørgensen, M. E, Jørgensen, T., Linneberg, A., Cornelis, M. C, van Dam, R. M, Hunter, D. J, Kraft, P., Sun, Q., Edkins, S., Owen, K. R, Perry, J. R B, Wood, A. R, Zeggini, E., Tajes-Fernandes, J., Abecasis, G. R, Bonnycastle, L. L, Chines, P. S, Stringham, H. M, Koistinen, H. A, Kinnunen, L., Sennblad, B., Mühleisen, T. W, Nöthen, M. M, Pechlivanis, S., Baldassarre, D., Gertow, K., Humphries, S. E, Tremoli, E., Klopp, N., Meyer, J., Steinbach, G., Wennauer, R., Eriksson, J. G, Mӓnnistö, S., Peltonen, L., Tikkanen, E., Charpentier, G., Eury, E., Lobbens, S., Gigante, B., Leander, K., McLeod, O., Bottinger, E. P, Gottesman, O., Ruderfer, D., Blüher, M., Kovacs, P., Tonjes, A., Maruthur, N. M, Scapoli, C., Erbel, R., Jöckel, K., Moebus, S., de Faire, U., Hamsten, A., Stumvoll, M., Deloukas, P., Donnelly, P. J, Frayling, T. M, Hattersley, A. T, Ripatti, S., Salomaa, V., Pedersen, N. L, Boehm, B. O, Bergman, R. N, Collins, F. S, Mohlke, K. L, Tuomilehto, J., Hansen, T., Pedersen, O., Barroso, I., Lannfelt, L., Ingelsson, E., Lind, L., Lindgren, C. M, Cauchi, S., Froguel, P., Loos, R. J F, Balkau, B., Boeing, H., Franks, P. W, Barricarte Gurrea, A., Palli, D., van der Schouw, Y. T, Altshuler, D., Groop, L. C, Langenberg, C., Wareham, N. J, Sijbrands, E., van Duijn, C. M, Florez, J. C, Meigs, J. B, Boerwinkle, E., Gieger, C., Strauch, K., Metspalu, A., Morris, A. D, Palmer, C. N A, Hu, F. B, Thorsteinsdottir, U., Stefansson, K., Dupuis, J., Morris, A. P, Boehnke, M., McCarthy, M. I, Prokopenko, I., & DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium Diabetes, 66(11):2888-2902, Nov, 2017. ![An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex To characterize 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 case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). 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 single nucleotide variants. 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.
@article{Scott:2017aa,
abstract = {To characterize 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 case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). 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 single nucleotide variants. 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.},
author = {Scott, Robert A and Scott, Laura J and M{\"a}gi, Reedik and Marullo, Letizia and Gaulton, Kyle J and Kaakinen, Marika and Pervjakova, Natalia and Pers, Tune H and Johnson, Andrew D and Eicher, John D and Jackson, Anne U and Ferreira, Teresa and Lee, Yeji and Ma, Clement and Steinthorsdottir, Valgerdur and Thorleifsson, Gudmar and Qi, Lu and Van Zuydam, Natalie R and Mahajan, Anubha and Chen, Han and Almgren, Peter and Voight, Ben F and Grallert, Harald and M{\"u}ller-Nurasyid, Martina and Ried, Janina S and Rayner, Nigel W and Robertson, Neil and Karssen, Lennart C and van Leeuwen, Elisabeth M and Willems, Sara M and Fuchsberger, Christian and Kwan, Phoenix and Teslovich, Tanya M and Chanda, Pritam and Li, Man and Lu, Yingchang and Dina, Christian and Thuillier, Dorothee and Yengo, Loic and Jiang, Longda and Sparso, Thomas and Kestler, Hans A and Chheda, Himanshu and Eisele, Lewin and Gustafsson, Stefan and Fr{\aa}nberg, Mattias and Strawbridge, Rona J and Benediktsson, Rafn and Hreidarsson, Astradur B and Kong, Augustine and Sigurðsson, Gunnar and Kerrison, Nicola D and Luan, Jian'an and Liang, Liming and Meitinger, Thomas and Roden, Michael and Thorand, Barbara and Esko, T{\~o}nu and Mihailov, Evelin and Fox, Caroline and Liu, Ching-Ti and Rybin, Denis and Isomaa, Bo and Lyssenko, Valeriya and Tuomi, Tiinamaija and Couper, David J and Pankow, James S and Grarup, Niels and Have, Christian T and J{\o}rgensen, Marit E and J{\o}rgensen, Torben and Linneberg, Allan and Cornelis, Marilyn C and van Dam, Rob M and Hunter, David J and Kraft, Peter and Sun, Qi and Edkins, Sarah and Owen, Katharine R and Perry, John R B and Wood, Andrew R and Zeggini, Eleftheria and Tajes-Fernandes, Juan and Abecasis, Goncalo R and Bonnycastle, Lori L and Chines, Peter S and Stringham, Heather M and Koistinen, Heikki A and Kinnunen, Leena and Sennblad, Bengt and M{\"u}hleisen, Thomas W and N{\"o}then, Markus M and Pechlivanis, Sonali and Baldassarre, Damiano and Gertow, Karl and Humphries, Steve E and Tremoli, Elena and Klopp, Norman and Meyer, Julia and Steinbach, Gerald and Wennauer, Roman and Eriksson, Johan G and Mӓnnist{\"o}, Satu and Peltonen, Leena and Tikkanen, Emmi and Charpentier, Guillaume and Eury, Elodie and Lobbens, St{\'e}phane and Gigante, Bruna and Leander, Karin and McLeod, Olga and Bottinger, Erwin P and Gottesman, Omri and Ruderfer, Douglas and Bl{\"u}her, Matthias and Kovacs, Peter and Tonjes, Anke and Maruthur, Nisa M and Scapoli, Chiara and Erbel, Raimund and J{\"o}ckel, Karl-Heinz and Moebus, Susanne and de Faire, Ulf and Hamsten, Anders and Stumvoll, Michael and Deloukas, Panagiotis and Donnelly, Peter J and Frayling, Timothy M and Hattersley, Andrew T and Ripatti, Samuli and Salomaa, Veikko and Pedersen, Nancy L and Boehm, Bernhard O and Bergman, Richard N and Collins, Francis S and Mohlke, Karen L and Tuomilehto, Jaakko and Hansen, Torben and Pedersen, Oluf and Barroso, In{\^e}s and Lannfelt, Lars and Ingelsson, Erik and Lind, Lars and Lindgren, Cecilia M and Cauchi, Stephane and Froguel, Philippe and Loos, Ruth J F and Balkau, Beverley and Boeing, Heiner and Franks, Paul W and Barricarte Gurrea, Aurelio and Palli, Domenico and van der Schouw, Yvonne T and Altshuler, David and Groop, Leif C and Langenberg, Claudia and Wareham, Nicholas J and Sijbrands, Eric and van Duijn, Cornelia M and Florez, Jose C and Meigs, James B and Boerwinkle, Eric and Gieger, Christian and Strauch, Konstantin and Metspalu, Andres and Morris, Andrew D and Palmer, Colin N A and Hu, Frank B and Thorsteinsdottir, Unnur and Stefansson, Kari and Dupuis, Jos{\'e}e and Morris, Andrew P and Boehnke, Michael and McCarthy, Mark I and Prokopenko, Inga and {DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium}},
date-added = {2024-05-19 21:02:35 -0400},
date-modified = {2024-05-19 21:02:35 -0400},
doi = {10.2337/db16-1253},
journal = {Diabetes},
journal-full = {Diabetes},
mesh = {Diabetes Mellitus, Type 2; Gene Expression Regulation; Genetic Variation; Genome-Wide Association Study; Humans; White People},
month = {Nov},
number = {11},
pages = {2888-2902},
pmc = {PMC5652602},
pmid = {28566273},
url = {https://pubmed.ncbi.nlm.nih.gov/28566273/},
pst = {ppublish},
title = {An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans},
volume = {66},
year = {2017},
bdsk-url-1 = {https://doi.org/10.2337/db16-1253}}
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multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). 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 single nucleotide variants. 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.},\n\tauthor = {Scott, Robert A and Scott, Laura J and M{\\\"a}gi, Reedik and Marullo, Letizia and Gaulton, Kyle J and Kaakinen, Marika and Pervjakova, Natalia and Pers, Tune H and Johnson, Andrew D and Eicher, John D and Jackson, Anne U and Ferreira, Teresa and Lee, Yeji and Ma, Clement and Steinthorsdottir, Valgerdur and Thorleifsson, Gudmar and Qi, Lu and Van Zuydam, Natalie R and Mahajan, Anubha and Chen, Han and Almgren, Peter and Voight, Ben F and Grallert, Harald and M{\\\"u}ller-Nurasyid, Martina and Ried, Janina S and Rayner, Nigel W and Robertson, Neil and Karssen, Lennart C and van Leeuwen, Elisabeth M and Willems, Sara M and Fuchsberger, Christian and Kwan, Phoenix and Teslovich, Tanya M and Chanda, Pritam and Li, Man and Lu, Yingchang and Dina, Christian and Thuillier, Dorothee and Yengo, Loic and Jiang, Longda and Sparso, Thomas and Kestler, Hans A and Chheda, Himanshu and Eisele, Lewin and Gustafsson, Stefan and Fr{\\aa}nberg, Mattias and Strawbridge, Rona J and Benediktsson, Rafn and Hreidarsson, Astradur B and Kong, Augustine and Sigurðsson, Gunnar and Kerrison, Nicola D and Luan, Jian'an and Liang, Liming and Meitinger, Thomas and Roden, Michael and Thorand, Barbara and Esko, T{\\~o}nu and Mihailov, Evelin and Fox, Caroline and Liu, Ching-Ti and Rybin, Denis and Isomaa, Bo and Lyssenko, Valeriya and Tuomi, Tiinamaija and Couper, David J and Pankow, James S and Grarup, Niels and Have, Christian T and J{\\o}rgensen, Marit E and J{\\o}rgensen, Torben and Linneberg, Allan and Cornelis, Marilyn C and van Dam, Rob M and Hunter, David J and Kraft, Peter and Sun, Qi and Edkins, Sarah and Owen, Katharine R and Perry, John R B and Wood, Andrew R and Zeggini, Eleftheria and Tajes-Fernandes, Juan and Abecasis, Goncalo R and Bonnycastle, Lori L and Chines, Peter S and Stringham, Heather M and Koistinen, Heikki A and Kinnunen, Leena and Sennblad, Bengt and M{\\\"u}hleisen, Thomas W and N{\\\"o}then, Markus M and Pechlivanis, Sonali and Baldassarre, Damiano and Gertow, Karl and Humphries, Steve E and Tremoli, Elena and Klopp, Norman and Meyer, Julia and Steinbach, Gerald and Wennauer, Roman and Eriksson, Johan G and Mӓnnist{\\\"o}, Satu and Peltonen, Leena and Tikkanen, Emmi and Charpentier, Guillaume and Eury, Elodie and Lobbens, St{\\'e}phane and Gigante, Bruna and Leander, Karin and McLeod, Olga and Bottinger, Erwin P and Gottesman, Omri and Ruderfer, Douglas and Bl{\\\"u}her, Matthias and Kovacs, Peter and Tonjes, Anke and Maruthur, Nisa M and Scapoli, Chiara and Erbel, Raimund and J{\\\"o}ckel, Karl-Heinz and Moebus, Susanne and de Faire, Ulf and Hamsten, Anders and Stumvoll, Michael and Deloukas, Panagiotis and Donnelly, Peter J and Frayling, Timothy M and Hattersley, Andrew T and Ripatti, Samuli and Salomaa, Veikko and Pedersen, Nancy L and Boehm, Bernhard O and Bergman, Richard N and Collins, Francis S and Mohlke, Karen L and Tuomilehto, Jaakko and Hansen, Torben and Pedersen, Oluf and Barroso, In{\\^e}s and Lannfelt, Lars and Ingelsson, Erik and Lind, Lars and Lindgren, Cecilia M and Cauchi, Stephane and Froguel, Philippe and Loos, Ruth J F and Balkau, Beverley and Boeing, Heiner and Franks, Paul W and Barricarte Gurrea, Aurelio and Palli, Domenico and van der Schouw, Yvonne T and Altshuler, David and Groop, Leif C and Langenberg, Claudia and Wareham, Nicholas J and Sijbrands, Eric and van Duijn, Cornelia M and Florez, Jose C and Meigs, James B and Boerwinkle, Eric and Gieger, Christian and Strauch, Konstantin and Metspalu, Andres and Morris, Andrew D and Palmer, Colin N A and Hu, Frank B and Thorsteinsdottir, Unnur and Stefansson, Kari and Dupuis, Jos{\\'e}e and Morris, Andrew P and Boehnke, Michael and McCarthy, Mark I and Prokopenko, Inga and {DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium}},\n\tdate-added = {2024-05-19 21:02:35 -0400},\n\tdate-modified = {2024-05-19 21:02:35 -0400},\n\tdoi = {10.2337/db16-1253},\n\tjournal = {Diabetes},\n\tjournal-full = {Diabetes},\n\tmesh = {Diabetes Mellitus, Type 2; Gene Expression Regulation; Genetic Variation; Genome-Wide Association Study; Humans; White People},\n\tmonth = {Nov},\n\tnumber = {11},\n\tpages = {2888-2902},\n\tpmc = {PMC5652602},\n\tpmid = {28566273},\n\turl = {https://pubmed.ncbi.nlm.nih.gov/28566273/},\n\tpst = {ppublish},\n\ttitle = {An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans},\n\tvolume = {66},\n\tyear = {2017},\n\tbdsk-url-1 = {https://doi.org/10.2337/db16-1253}}\n\n","author_short":["Scott, R. 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I","Prokopenko, I.","DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium"],"key":"Scott:2017aa","id":"Scott:2017aa","bibbaseid":"scott-scott-mgi-marullo-gaulton-kaakinen-pervjakova-pers-etal-anexpandedgenomewideassociationstudyoftype2diabetesineuropeans-2017","role":"author","urls":{"Paper":"https://pubmed.ncbi.nlm.nih.gov/28566273/"},"metadata":{"authorlinks":{}},"downloads":0,"html":""},"bibtype":"article","biburl":"https://bibbase.org/network/files/gqwqyBJuHtD7EvhhG","dataSources":["Y9DJHroPCz3Lqc5T2"],"keywords":[],"search_terms":["expanded","genome","wide","association","study","type","diabetes","europeans","scott","scott","mägi","marullo","gaulton","kaakinen","pervjakova","pers","johnson","eicher","jackson","ferreira","lee","ma","steinthorsdottir","thorleifsson","qi","van zuydam","mahajan","chen","almgren","voight","grallert","müller-nurasyid","ried","rayner","robertson","karssen","van leeuwen","willems","fuchsberger","kwan","teslovich","chanda","li","lu","dina","thuillier","yengo","jiang","sparso","kestler","chheda","eisele","gustafsson","frånberg","strawbridge","benediktsson","hreidarsson","kong","sigurðsson","kerrison","luan","liang","meitinger","roden","thorand","esko","mihailov","fox","liu","rybin","isomaa","lyssenko","tuomi","couper","pankow","grarup","have","jørgensen","jørgensen","linneberg","cornelis","van dam","hunter","kraft","sun","edkins","owen","perry","wood","zeggini","tajes-fernandes","abecasis","bonnycastle","chines","stringham","koistinen","kinnunen","sennblad","mühleisen","nöthen","pechlivanis","baldassarre","gertow","humphries","tremoli","klopp","meyer","steinbach","wennauer","eriksson","mӓnnistö","peltonen","tikkanen","charpentier","eury","lobbens","gigante","leander","mcleod","bottinger","gottesman","ruderfer","blüher","kovacs","tonjes","maruthur","scapoli","erbel","jöckel","moebus","de faire","hamsten","stumvoll","deloukas","donnelly","frayling","hattersley","ripatti","salomaa","pedersen","boehm","bergman","collins","mohlke","tuomilehto","hansen","pedersen","barroso","lannfelt","ingelsson","lind","lindgren","cauchi","froguel","loos","balkau","boeing","franks","barricarte gurrea","palli","van der schouw","altshuler","groop","langenberg","wareham","sijbrands","van duijn","florez","meigs","boerwinkle","gieger","strauch","metspalu","morris","palmer","hu","thorsteinsdottir","stefansson","dupuis","morris","boehnke","mccarthy","prokopenko","diabetes genetics replication and meta-analysis (diagram) consortium"],"title":"An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans","year":2017}