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- Dokumenttyp:
- Journal Article
- Autor(en):
- Titel:
- Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps.
- 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).
- Zeitschriftentitel:
- Nat Genet
- Jahr:
- 2018
- Band / Volume:
- 50
- Heft / Issue:
- 11
- Seitenangaben Beitrag:
- 1505-1513
- Volltext / DOI:
- doi:10.1038/s41588-018-0241-6
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/30297969
- Print-ISSN:
- 1061-4036
- TUM Einrichtung:
- Institut für Humangenetik
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