dc.contributor.author | Murray, A | |
dc.contributor.author | Freathy, RM | |
dc.contributor.author | Weedon, MN | |
dc.contributor.author | Hattersley, AT | |
dc.contributor.author | Hayward, C | |
dc.contributor.author | Machann, J | |
dc.contributor.author | Häring, HU | |
dc.contributor.author | Franks, P | |
dc.contributor.author | de Mutsert, R | |
dc.contributor.author | Pearson, E | |
dc.contributor.author | Stefan, N | |
dc.contributor.author | Frayling, TM | |
dc.contributor.author | Allebrandt, KV | |
dc.contributor.author | Bell, JD | |
dc.contributor.author | Blakemore, AI | |
dc.contributor.author | Yaghootkar, H | |
dc.date.accessioned | 2019-01-22T13:51:40Z | |
dc.date.issued | 2018-10-23 | |
dc.description.abstract | Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14, and IRS1, whereas the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots. | en_GB |
dc.description.sponsorship | Diabetes Research and Wellness Foundation | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Royal Society | en_GB |
dc.description.sponsorship | European Research Council | en_GB |
dc.description.sponsorship | Diabetes UK | en_GB |
dc.description.sponsorship | German Federal Ministry of Education and Research | en_GB |
dc.description.sponsorship | German Research Foundation | en_GB |
dc.description.sponsorship | Dutch Science Organization | en_GB |
dc.description.sponsorship | Chief Scientist Office of the Scottish Government Health Directorates | en_GB |
dc.description.sponsorship | Scottish Funding Council | en_GB |
dc.identifier.citation | Vol. 68 (1), pp. 207 - 219 | en_GB |
dc.identifier.doi | 10.2337/db18-0708 | |
dc.identifier.grantnumber | MR/M005070/1 | en_GB |
dc.identifier.grantnumber | 104150/Z/14/Z | en_GB |
dc.identifier.grantnumber | 323195:GLUCOSEGENES-FP7-IDEAS-ERC | en_GB |
dc.identifier.grantnumber | 17/0005594 | en_GB |
dc.identifier.grantnumber | 01GI0925 | en_GB |
dc.identifier.grantnumber | KFO114 | en_GB |
dc.identifier.grantnumber | 916.14.023 | en_GB |
dc.identifier.grantnumber | CZD/16/6 | en_GB |
dc.identifier.grantnumber | HR03006 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/35553 | |
dc.language.iso | en | en_GB |
dc.publisher | American Diabetes Association | en_GB |
dc.rights | © 2018 by the American Diabetes Association. http://www.diabetesjournals.org/content/license
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license. | |
dc.title | Genome-wide and abdominal MRI data provide evidence that a genetically determined favorable adiposity phenotype is characterized by lower ectopic liver fat and lower risk of type 2 diabetes, heart disease, and hypertension | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-01-22T13:51:40Z | |
dc.identifier.issn | 0012-1797 | |
dc.description | This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this record | en_GB |
dc.identifier.journal | Diabetes | en_GB |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dcterms.dateAccepted | 2018-10-12 | |
exeter.funder | ::Wellcome Trust | en_GB |
exeter.funder | ::Diabetes Research and Wellness Foundation | en_GB |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2018-10-12 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-01-22T13:43:09Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2019-01-22T13:51:50Z | |
refterms.panel | A | en_GB |