@article{3085494,
    title = "Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps",
    author = "Mahajan, A. and Taliun, D. and Thurner, M. and Robertson, N.R. and Torres, J.M. and Rayner, N.W. and Payne, A.J. and Steinthorsdottir, V. and Scott, R.A. and Grarup, N. and Cook, J.P. and Schmidt, E.M. and Wuttke, M. and Sarnowski, C. and Mägi, R. and Nano, J. and Gieger, C. and Trompet, S. and Lecoeur, C. and Preuss, M.H. and Prins, B.P. and Guo, X. and Bielak, L.F. and Below, J.E. and Bowden, D.W. and Chambers, J.C. and Kim, Y.J. and Ng, M.C.Y. and Petty, L.E. and Sim, X. and Zhang, W. and Bennett, A.J. and Bork-Jensen, J. and Brummett, C.M. and Canouil, M. and Ec kardt, K.-U. and Fischer, K. and Kardia, S.L.R. and Kronenberg, F. and Läll, K. and Liu, C.-T. and Locke, A.E. and Luan, J. and Ntalla, I. and Nylander, V. and Schönherr, S. and Schurmann, C. and Yengo, L. and Bottinger, E.P. and Brandslund, I. and Christensen, C. and Dedoussis, G. and Florez, J.C. and Ford, I. and Franco, O.H. and Frayling, T.M. and Giedraitis, V. and Hackinger, S. and Hattersley, A.T. and Herder, C. and Ikram, M.A. and Ingelsson, M. and Jørgensen, M.E. and Jørgensen, T. and Kriebel, J. and Kuusisto, J. and Ligthart, S. and Lindgren, C.M. and Linneberg, A. and Lyssenko, V. and Mamakou, V. and Meitinger, T. and Mohlke, K.L. and Morris, A.D. and Nadkarni, G. and Pankow, J.S. and Peters, A. and Sattar, N. and Stančáková, A. and Strauch, K. and Taylor, K.D. and Thorand, B. and Thorleifsson, G. and Thorsteinsdottir, U. and Tuomilehto, J. and Witte, D.R. and Dupuis, J. and Peyser, P.A. and Zeggini, E. and Loos, R.J.F. and Froguel, P. and Ingelsson, E. and Lind, L. and Groop, L. and Laakso, M. and Collins, F.S. and Jukema, J.W. and Palmer, C.N.A. and Grallert, H. and Metspalu, A. and Dehghan, A. and Köttgen, A. and Abecasis, G.R. and Meigs, J.B. and Rotter, J.I. and Marchini, J. and Pedersen, O. and Hansen, T. and Langenberg, C. and Wareham, N.J. and Stefansson, K. and Gloyn, A.L. and Morris, A.P. and Boehnke, M. and McCarthy, M.I.",
    journal = "Nature Genetics",
    year = "2018",
    volume = "50",
    number = "11",
    pages = "1505-1513",
    publisher = "Nature Publishing Group",
    issn = "1061-4036, 1546-1718",
    doi = "10.1038/s41588-018-0241-6",
    keywords = "adult;  Article;  body mass;  controlled study;  disease predisposition;  epigenetics;  European;  female;  FTO gene;  gene;  gene frequency;  gene locus;  gene mapping;  genetic association;  genetic predisposition;  genetic risk;  genetic susceptibility;  genetic trait;  genetic variability;  genome-wide association study;  genotype;  gnpda2 gene;  haplotype;  heritability;  human;  major clinical study;  male;  mc4r gene;  middle aged;  non insulin dependent diabetes mellitus;  priority journal;  sec16b gene;  sex difference;  single nucleotide polymorphism;  tmem18 gene;  case control study;  Caucasian;  chromosomal mapping;  gene linkage disequilibrium;  gene locus;  genetic epigenesis;  genetics;  genome-wide association study;  high throughput screening;  human genome;  meta analysis (topic);  metabolism;  non insulin dependent diabetes mellitus;  pancreas islet;  pathology;  procedures;  sex factor, Body Mass Index;  Case-Control Studies;  Chromosome Mapping;  Diabetes Mellitus, Type 2;  Epigenesis, Genetic;  European Continental Ancestry Group;  Female;  Gene Frequency;  Genetic Loci;  Genetic Predisposition to Disease;  Genome, Human;  Genome-Wide Association Study;  High-Throughput Screening Assays;  Humans;  Islets of Langerhans;  Linkage Disequilibrium;  Male;  Meta-Analysis as Topic;  Polymorphism, Single Nucleotide;  Sex Factors",
    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). © 2018, The Author(s), under exclusive licence to Springer Nature America, Inc."
}