naa a22 4500 510779441 CHVBK 20180411083242.0 cr unu---uuuuu 180411e20131201xx s 000 0 eng 10.1007/s11892-013-0429-1 doi (NATIONALLICENCE)springer-10.1007/s11892-013-0429-1 Bridging the Gap Between Genetic Associations and Molecular Mechanisms for Type 2 Diabetes [Elektronische Daten] [Hui Ng, Anna Gloyn] Type 2 diabetes is a global pandemic for which there is currently no disease-modifying treatment. New and targeted therapeutics are greatly needed, but progress in identifying novel targets for therapeutic intervention is severely hampered by poor understanding of disease pathogenesis. Over the past 6years, the success of genome-wide association studies has led to an unprecedented increase in the number of loci robustly associating with type 2 diabetes risk. Each of these signals offers the opportunity to uncover biological insights into disease pathogenesis, which, if harnessed effectively, hold the promise to deliver new pathways for therapeutic intervention, strategies for patient stratification, and potentially, biomarkers for identifying those at greatest risk of developing diabetes. We review the progress that has been made and the approaches being adopted and discuss the inherent challenges in moving from association signals, which largely map to poorly annotated sequence, to transcripts, mechanisms, and disease biology. Springer Science+Business Media New York, 2013 Type 2 diabetes nationallicence Genome-wide association studies nationallicence Association signal nationallicence Molecular mechanisms nationallicence Beta cell nationallicence Pancreatic islet nationallicence Functional characterization nationallicence Targeted sequencing nationallicence eQTL nationallicence miRNA nationallicence DNA methylation nationallicence Knockout mice nationallicence Human model nationallicence Ng Hui Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, OX3 7LE, Oxford, UK aut Gloyn Anna Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, OX3 7LE, Oxford, UK aut Current Diabetes Reports Springer US; http://www.springer-ny.com 13/6(2013-12-01), 778-785 1534-4827 13:6<778 2013 13 11892 https://doi.org/10.1007/s11892-013-0429-1 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11892-013-0429-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ng Hui Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, OX3 7LE, Oxford, UK aut NATIONALLICENCE 700 1- Gloyn Anna Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, OX3 7LE, Oxford, UK aut NATIONALLICENCE 773 0- Current Diabetes Reports Springer US; http://www.springer-ny.com 13/6(2013-12-01), 778-785 1534-4827 13:6<778 2013 13 11892 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer