| Literature DB >> 30297969 |
Anubha Mahajan1,2, Daniel Taliun3, Matthias Thurner4,5, Neil R Robertson4,5, Jason M Torres4, N William Rayner4,5,6, Anthony J Payne4, Valgerdur Steinthorsdottir7, Robert A Scott8, Niels Grarup9, James P Cook10, Ellen M Schmidt3, Matthias Wuttke11, Chloé Sarnowski12, Reedik Mägi13, Jana Nano14, Christian Gieger15,16, Stella Trompet17,18, Cécile Lecoeur19, Michael H Preuss20, Bram Peter Prins6, Xiuqing Guo21, Lawrence F Bielak22, Jennifer E Below23, Donald W Bowden24,25,26, John Campbell Chambers27,28,29,30,31, Young Jin Kim32, Maggie C Y Ng24,25,26, Lauren E Petty23, Xueling Sim33, Weihua Zhang27,28, Amanda J Bennett5, Jette Bork-Jensen9, Chad M Brummett34, Mickaël Canouil19, Kai-Uwe Ec Kardt35, Krista Fischer13, Sharon L R Kardia22, Florian Kronenberg36, Kristi Läll13,37, Ching-Ti Liu12, Adam E Locke38,39, Jian'an Luan8, Ioanna Ntalla40, Vibe Nylander5, Sebastian Schönherr36, Claudia Schurmann20, Loïc Yengo19, Erwin P Bottinger20, Ivan Brandslund41,42, Cramer Christensen43, George Dedoussis44, Jose C Florez45,46,47,48, Ian Ford49, Oscar H Franco14, Timothy M Frayling50, Vilmantas Giedraitis51, Sophie Hackinger6, Andrew T Hattersley52, Christian Herder16,53, M Arfan Ikram14, Martin Ingelsson51, Marit E Jørgensen54,55, Torben Jørgensen56,57,58, Jennifer Kriebel15,16, Johanna Kuusisto59, Symen Ligthart14, Cecilia M Lindgren4,60,61, Allan Linneberg56,62,63, Valeriya Lyssenko64,65, Vasiliki Mamakou66, Thomas Meitinger67,68,69, Karen L Mohlke70, Andrew D Morris71,72, Girish Nadkarni73, James S Pankow74, Annette Peters16,69,75, Naveed Sattar76, Alena Stančáková59, Konstantin Strauch77,78, Kent D Taylor21, Barbara Thorand16,75, Gudmar Thorleifsson7, Unnur Thorsteinsdottir7,79, Jaakko Tuomilehto80,81,82,83, Daniel R Witte84,85, Josée Dupuis12,86, Patricia A Peyser22, Eleftheria Zeggini6, Ruth J F Loos20,87, Philippe Froguel19,88, Erik Ingelsson89,90, Lars Lind91, Leif Groop64,92, Markku Laakso59, Francis S Collins93, J Wouter Jukema18, Colin N A Palmer94, Harald Grallert15,16,95,96, Andres Metspalu13, Abbas Dehghan14,27,31, Anna Köttgen11, Goncalo R Abecasis3, James B Meigs45,48,97, Jerome I Rotter21,98, Jonathan Marchini4,99, Oluf Pedersen9, Torben Hansen9,100, Claudia Langenberg8, Nicholas J Wareham8, Kari Stefansson7,79, Anna L Gloyn4,5,101, Andrew P Morris4,10,13, Michael Boehnke3, Mark I McCarthy102,103,104.
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).Entities:
Mesh：
Year: 2018 PMID： 30297969 PMCID： PMC6287706 DOI： 10.1038/s41588-018-0241-6
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330