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dc.contributor.author | Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) | |
dc.date.accessioned | 2021-06-10T09:22:44Z | |
dc.date.issued | 2021-05-31 | |
dc.description.abstract | Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. | en_GB |
dc.identifier.citation | Vol. 53, pp. 840–860 | en_GB |
dc.identifier.doi | 10.1038/s41588-021-00852-9 | |
dc.identifier.uri | http://hdl.handle.net/10871/125997 | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Research | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/34059833 | en_GB |
dc.relation.url | https://doi.org/10.5281/zenodo.4607311 | en_GB |
dc.relation.url | https://www.magicinvestigators.org/ | en_GB |
dc.relation.url | https://www.ebi.ac.uk/gwas/ | en_GB |
dc.rights.embargoreason | Under embargo until 30 November 2021 in compliance with publisher policy | en_GB |
dc.rights | © The Author(s), under exclusive licence to Springer Nature America, Inc. 2021 | en_GB |
dc.title | The trans-ancestral genomic architecture of glycemic traits | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2021-06-10T09:22:44Z | |
exeter.place-of-publication | United States | en_GB |
dc.description | This is the author accepted manuscript. The final version is available from nature Research via the DOI in this record | en_GB |
dc.description | Note: There are differences between the text of the author accepted manuscript in this record and that of the final published version. this is due to a large number of textual changes and cuts made by the authors after official final acceptance, at the request of the journal editorial office. | en_GB |
dc.description | Code availability:
Source code implementing the methods described in the paper are publicly available at https://doi.org/10.5281/zenodo.4607311. | en_GB |
dc.description | Data availability: Ancestry-specific and overall meta-analysis summary level results are available through the MAGIC website (https://www.magicinvestigators.org/). Summary statistics are also available through the GWAS catalog (https://www.ebi.ac.uk/gwas/) with the following accession codes: GCST90002225, GCST90002226, GCST90002227, GCST90002228, GCST90002229, GCST90002230, GCST90002231, GCST90002232, GCST90002233, GCST90002234, GCST90002235, GCST90002236, GCST90002237, GCST90002238, GCST90002239, GCST90002240, GCST90002241, GCST90002242, GCST90002243, GCST90002244, GCST90002245, GCST90002246, GCST90002247 and GCST90002248. | en_GB |
dc.identifier.eissn | 1546-1718 | |
dc.identifier.journal | Nature Genetics | en_GB |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dcterms.dateAccepted | 2021-03-22 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2021-05-31 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2021-06-10T09:19:34Z | |
refterms.versionFCD | AM | |
refterms.panel | A | en_GB |