Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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).

Original publication

DOI

10.1038/s41588-018-0241-6

Type

Journal article

Journal

Nature genetics

Publication Date

11/2018

Volume

50

Pages

1505 - 1513

Addresses

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. anubha@well.ox.ac.uk.

Keywords

Islets of Langerhans, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Body Mass Index, Case-Control Studies, Chromosome Mapping, Sex Factors, Epigenesis, Genetic, Gene Frequency, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Genome, Human, European Continental Ancestry Group, Female, Male, Meta-Analysis as Topic, Genome-Wide Association Study, Genetic Loci, High-Throughput Screening Assays