Mahajan, Anubha; Taliun, Daniel; Thurner, Matthias; Robertson, Neil R.; Torres, Jason M.; Rayner, N. William; Payne, Anthony J.; Steinthorsdottir, Valgerdur; Scott, Robert A.; Grarup, Niels; Cook, James P.; Schmidt, Ellen M.; Wuttke, Matthias; Sarnowski, Chloe; Magill, Reedik; Nano, Jana; Gieger, Christian; Trompet, Stella; Lecoeur, Cecile; Preuss, Michael H.; Prins, Bram Peter; Guo, Xiuqing; Bielak, Lawrence F.; Below, Jennifer E.; Bowden, Donald W.; Chambers, John Campbell; Kim, Young Jin; Ng, Maggie C. Y.; Petty, Lauren E.; Sim, Xueling; Zhang, Weihua; Bennett, Amanda J.; Bork-Jensen, Jette; Brummett, Chad M.; Canouil, Mickael; Kardt, Kai-Uwe Ec; Fischer, Krista; Kardia, Sharon L. R.; Kronenberg, Florian; Lall, Kristi; Liu, Ching-Ti; Locke, Adam E.; Luan, Jian'an; Ntalla, Loanna; Nylander, Vibe; Schönherr, Sebastian; Schurmann, Claudia; Yengo, Loic; Bottinger, Erwin P.; Brandslund, Ivan; Christensen, Cramer; Dedoussis, George; Florez, Jose C.; Ford, Ian; France, Oscar H.; Frayling, Timothy M.; Giedraitis, Vilmantas; Hackinger, Sophie; Hattersley, Andrew T.; Herder, Christian; Ikram, M. Arfan; Ingelsson, Martin; Jorgensen, Marit E.; Jorgensen, Torben; Kriebel, Jennifer; Kuusisto, Johanna; Ligthart, Symen; Lindgren, Cecilia M.; Linneberg, Allan; Lyssenko, Valeriya; Mamakou, Vasiliki; Meitinger, Thomas; Mohlke, Karen L.; Morris, Andrew D.; Nadkarni, Girish; Pankow, James S.; Peters, Annette; Sattar, Naveed; Stancakova, Alena; Strauch, Konstantin; Taylor, Kent D.; Thorand, Barbara; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tuomilehto, Jaakko; Witte, Daniel R.; Dupuis, Josee; Peyser, Patricia A.; Zeggini, Eleftheria; Loos, Ruth J. F.; Froguel, Philippe; Ingelsson, Erik; Lind, Lars; Groop, Leif; Laakso, Markku; Collins, Francis S.; Jukema, J. Wouter; Palmer, Colin N. A.; Grallert, Harald; Metspalu, Andres; Dehghan, Abbas; Koettgen, Anna; Abecasis, Goncalo R.; Meigs, James B.; Rotter, Jerome; Marchini, Jonathan; Pedersen, Oluf; Hansen, Torben; Langenberg, Claudia; Wareham, Nicholas J.; Stefansson, Kari; Gloyn, Anna L.; Morris, Andrew P.; Böhnke, Michael; McCarthy, Mark (2018): Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. In: Nature Genetics, Vol. 50, No. 11: pp. 1505-1513 |
Abstract
We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci,135 newly implicated in T2D predisposition, comprising 403 distinct association signals);(ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%,14 with estimated allelic odds ratio >2);(iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA));(iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73);(v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants);and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk;individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).
Item Type: | Journal article |
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Faculties: | Medicine > Institute for Medical Information Processing, Biometry and Epidemiology |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 1061-4036 |
Language: | English |
ID Code: | 62909 |
Deposited On: | 19. Jul 2019 12:11 |
Last Modified: | 19. Jul 2019 12:11 |
- BASE
- Mahajan, Anubha
- Taliun, Daniel
- Thurner, Matthias
- Robertson, Neil R.
- Torres, Jason M.
- Rayner, N. William
- Payne, Anthony J.
- Steinthorsdottir, Valgerdur
- Scott, Robert A.
- Grarup, Niels
- Cook, James P.
- Schmidt, Ellen M.
- Wuttke, Matthias
- Sarnowski, Chloe
- Magill, Reedik
- Nano, Jana
- Gieger, Christian
- Trompet, Stella
- Lecoeur, Cecile
- Preuss, Michael H.
- Prins, Bram Peter
- Guo, Xiuqing
- Bielak, Lawrence F.
- Below, Jennifer E.
- Bowden, Donald W.
- Chambers, John Campbell
- Kim, Young Jin
- Ng, Maggie C. Y.
- Petty, Lauren E.
- Sim, Xueling
- Zhang, Weihua
- Bennett, Amanda J.
- Bork-Jensen, Jette
- Brummett, Chad M.
- Canouil, Mickael
- Kardt, Kai-Uwe Ec
- Fischer, Krista
- Kardia, Sharon L. R.
- Kronenberg, Florian
- Lall, Kristi
- Liu, Ching-Ti
- Locke, Adam E.
- Luan, Jian'an
- Ntalla, Loanna
- Nylander, Vibe
- Schönherr, Sebastian
- Schurmann, Claudia
- Yengo, Loic
- Bottinger, Erwin P.
- Brandslund, Ivan
- Christensen, Cramer
- Dedoussis, George
- Florez, Jose C.
- Ford, Ian
- France, Oscar H.
- Frayling, Timothy M.
- Giedraitis, Vilmantas
- Hackinger, Sophie
- Hattersley, Andrew T.
- Herder, Christian
- Ikram, M. Arfan
- Ingelsson, Martin
- Jorgensen, Marit E.
- Jorgensen, Torben
- Kriebel, Jennifer
- Kuusisto, Johanna
- Ligthart, Symen
- Lindgren, Cecilia M.
- Linneberg, Allan
- Lyssenko, Valeriya
- Mamakou, Vasiliki
- Meitinger, Thomas
- Mohlke, Karen L.
- Morris, Andrew D.
- Nadkarni, Girish
- Pankow, James S.
- Peters, Annette
- Sattar, Naveed
- Stancakova, Alena
- Strauch, Konstantin
- Taylor, Kent D.
- Thorand, Barbara
- Thorleifsson, Gudmar
- Thorsteinsdottir, Unnur
- Tuomilehto, Jaakko
- Witte, Daniel R.
- Dupuis, Josee
- Peyser, Patricia A.
- Zeggini, Eleftheria
- Loos, Ruth J. F.
- Froguel, Philippe
- Ingelsson, Erik
- Lind, Lars
- Groop, Leif
- Laakso, Markku
- Collins, Francis S.
- Jukema, J. Wouter
- Palmer, Colin N. A.
- Grallert, Harald
- Metspalu, Andres
- Dehghan, Abbas
- Koettgen, Anna
- Abecasis, Goncalo R.
- Meigs, James B.
- Rotter, Jerome
- Marchini, Jonathan
- Pedersen, Oluf
- Hansen, Torben
- Langenberg, Claudia
- Wareham, Nicholas J.
- Stefansson, Kari
- Gloyn, Anna L.
- Morris, Andrew P.
- Böhnke, Michael
- McCarthy, Mark
- Google Scholar
- Mahajan, Anubha
- Taliun, Daniel
- Thurner, Matthias
- Robertson, Neil R.
- Torres, Jason M.
- Rayner, N. William
- Payne, Anthony J.
- Steinthorsdottir, Valgerdur
- Scott, Robert A.
- Grarup, Niels
- Cook, James P.
- Schmidt, Ellen M.
- Wuttke, Matthias
- Sarnowski, Chloe
- Magill, Reedik
- Nano, Jana
- Gieger, Christian
- Trompet, Stella
- Lecoeur, Cecile
- Preuss, Michael H.
- Prins, Bram Peter
- Guo, Xiuqing
- Bielak, Lawrence F.
- Below, Jennifer E.
- Bowden, Donald W.
- Chambers, John Campbell
- Kim, Young Jin
- Ng, Maggie C. Y.
- Petty, Lauren E.
- Sim, Xueling
- Zhang, Weihua
- Bennett, Amanda J.
- Bork-Jensen, Jette
- Brummett, Chad M.
- Canouil, Mickael
- Kardt, Kai-Uwe Ec
- Fischer, Krista
- Kardia, Sharon L. R.
- Kronenberg, Florian
- Lall, Kristi
- Liu, Ching-Ti
- Locke, Adam E.
- Luan, Jian'an
- Ntalla, Loanna
- Nylander, Vibe
- Schönherr, Sebastian
- Schurmann, Claudia
- Yengo, Loic
- Bottinger, Erwin P.
- Brandslund, Ivan
- Christensen, Cramer
- Dedoussis, George
- Florez, Jose C.
- Ford, Ian
- France, Oscar H.
- Frayling, Timothy M.
- Giedraitis, Vilmantas
- Hackinger, Sophie
- Hattersley, Andrew T.
- Herder, Christian
- Ikram, M. Arfan
- Ingelsson, Martin
- Jorgensen, Marit E.
- Jorgensen, Torben
- Kriebel, Jennifer
- Kuusisto, Johanna
- Ligthart, Symen
- Lindgren, Cecilia M.
- Linneberg, Allan
- Lyssenko, Valeriya
- Mamakou, Vasiliki
- Meitinger, Thomas
- Mohlke, Karen L.
- Morris, Andrew D.
- Nadkarni, Girish
- Pankow, James S.
- Peters, Annette
- Sattar, Naveed
- Stancakova, Alena
- Strauch, Konstantin
- Taylor, Kent D.
- Thorand, Barbara
- Thorleifsson, Gudmar
- Thorsteinsdottir, Unnur
- Tuomilehto, Jaakko
- Witte, Daniel R.
- Dupuis, Josee
- Peyser, Patricia A.
- Zeggini, Eleftheria
- Loos, Ruth J. F.
- Froguel, Philippe
- Ingelsson, Erik
- Lind, Lars
- Groop, Leif
- Laakso, Markku
- Collins, Francis S.
- Jukema, J. Wouter
- Palmer, Colin N. A.
- Grallert, Harald
- Metspalu, Andres
- Dehghan, Abbas
- Koettgen, Anna
- Abecasis, Goncalo R.
- Meigs, James B.
- Rotter, Jerome
- Marchini, Jonathan
- Pedersen, Oluf
- Hansen, Torben
- Langenberg, Claudia
- Wareham, Nicholas J.
- Stefansson, Kari
- Gloyn, Anna L.
- Morris, Andrew P.
- Böhnke, Michael
- McCarthy, Mark