Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps
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, com...
| প্রধান লেখক: | , , , , , , , , , , , , , , |
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| বিন্যাস: | Journal article |
| প্রকাশিত: |
Springer Nature
2018
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| _version_ | 1826282791386480640 |
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| author | Mahajan, A Taliun, D Thurner, M Robertson, N Torres, J Rayner, N Payne, A Bennett, A Nylander, V Lindgren, C Marchini, J Gloyn, A Morris, A McCarthy, M al., E |
| author_facet | Mahajan, A Taliun, D Thurner, M Robertson, N Torres, J Rayner, N Payne, A Bennett, A Nylander, V Lindgren, C Marchini, J Gloyn, A Morris, A McCarthy, M al., E |
| author_sort | Mahajan, A |
| collection | OXFORD |
| description | 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). |
| first_indexed | 2024-03-07T00:49:11Z |
| format | Journal article |
| id | oxford-uuid:85c6768f-5bc8-48b6-ae4b-149d23bd3fb7 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T00:49:11Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:85c6768f-5bc8-48b6-ae4b-149d23bd3fb72022-03-26T21:59:45ZFine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome mapsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:85c6768f-5bc8-48b6-ae4b-149d23bd3fb7Symplectic Elements at OxfordSpringer Nature2018Mahajan, ATaliun, DThurner, MRobertson, NTorres, JRayner, NPayne, ABennett, ANylander, VLindgren, CMarchini, JGloyn, AMorris, AMcCarthy, Mal., EWe 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). |
| spellingShingle | Mahajan, A Taliun, D Thurner, M Robertson, N Torres, J Rayner, N Payne, A Bennett, A Nylander, V Lindgren, C Marchini, J Gloyn, A Morris, A McCarthy, M al., E Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps |
| title | Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps |
| title_full | Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps |
| title_fullStr | Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps |
| title_full_unstemmed | Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps |
| title_short | Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps |
| title_sort | fine mapping type 2 diabetes loci to single variant resolution using high density imputation and islet specific epigenome maps |
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