dc.contributor.author | Locke, JM | |
dc.contributor.author | Saint-Martin, C | |
dc.contributor.author | Laver, TW | |
dc.contributor.author | Patel, KA | |
dc.contributor.author | Wood, AR | |
dc.contributor.author | Sharp, SA | |
dc.contributor.author | Ellard, S | |
dc.contributor.author | Bellanné-Chantelot, C | |
dc.contributor.author | Hattersley, AT | |
dc.contributor.author | Harries, LW | |
dc.contributor.author | Weedon, MN | |
dc.date.accessioned | 2018-06-22T11:57:08Z | |
dc.date.issued | 2018-06-12 | |
dc.description.abstract | There is wide variation in the age at diagnosis of diabetes in individuals with Maturity-Onset Diabetes of the Young (MODY) due to a mutation in the HNF1A gene. We hypothesised that common variants at the HNF1A locus (rs1169288, I27L; rs1800574, A98V), which are associated with type 2 diabetes susceptibility, may modify age at diabetes diagnosis in HNF1A-MODY individuals. Meta-analysis of two independent cohorts, comprising 781 HNF1A-MODY individuals, found no significant associations between genotype and age at diagnosis. However after stratifying according to type of mutation (protein-truncating variant (PTV) or missense), we found each 27L allele to be associated with a 1.6 year decrease (95% CI -2.6, -0.7) in age at diagnosis, specifically in the subset (n=444) of HNF1A-MODY individuals with a PTV. The effect size was similar and significant across the two independent cohorts of HNF1A-MODY individuals. We report a robust genetic modifier of HNF1A-MODY age at diagnosis that further illustrates the strong effect of genetic variation within HNF1A upon diabetes phenotype. | en_GB |
dc.description.sponsorship | This article presents independent research funded by Medical Research Council grants to LWH (MR/J006777/1) and to MNW (MR/M0050701) and supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the Medical Research Council, NHS, the NIHR or the Department of Health. | en_GB |
dc.identifier.citation | Published online 12 June 2018 | en_GB |
dc.identifier.doi | 10.2337/db18-0133 | |
dc.identifier.uri | http://hdl.handle.net/10871/33272 | |
dc.language.iso | en | en_GB |
dc.publisher | American Diabetes Association | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/29895593 | en_GB |
dc.rights | © 2018, American Diabetes Association All rights reserved. | en_GB |
dc.title | The Common HNF1A Variant I27L is a Modifier of Age at Diabetes Diagnosis in HNF1A-MODY Individuals. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-06-22T11:57:08Z | |
exeter.place-of-publication | United States | en_GB |
dc.description | This is the author accepted manuscript. The final version is available from American Diabetes Association via the DOI in this record. | en_GB |
dc.identifier.journal | Diabetes | en_GB |