dc.contributor.author | Martin, S | |
dc.contributor.author | Cule, M | |
dc.contributor.author | Basty, N | |
dc.contributor.author | Tyrrell, J | |
dc.contributor.author | Beaumont, RN | |
dc.contributor.author | Wood, AR | |
dc.contributor.author | Frayling, TM | |
dc.contributor.author | Sorokin, E | |
dc.contributor.author | Whitcher, B | |
dc.contributor.author | Liu, Y | |
dc.contributor.author | Bell, JD | |
dc.contributor.author | Thomas, EL | |
dc.contributor.author | Yaghootkar, H | |
dc.date.accessioned | 2022-01-28T13:31:25Z | |
dc.date.issued | 2021-05-12 | |
dc.date.updated | 2022-01-28T12:40:56Z | |
dc.description.abstract | To understand the causal role of adiposity and ectopic fat in type 2 diabetes and cardiometabolic diseases, we aimed to identify two clusters of adiposity genetic variants: one with "adverse" metabolic effects (UFA) and the other with, paradoxically, "favorable" metabolic effects (FA). We performed a multivariate genome-wide association study using body fat percentage and metabolic biomarkers from UK Biobank and identified 38 UFA and 36 FA variants. Adiposity-increasing alleles were associated with an adverse metabolic profile, higher risk of disease, higher CRP, and higher fat in subcutaneous and visceral adipose tissue, liver, and pancreas for UFA and a favorable metabolic profile, lower risk of disease, higher CRP and higher subcutaneous adipose tissue but lower liver fat for FA. We detected no sexual dimorphism. The Mendelian randomization studies provided evidence for a risk-increasing effect of UFA and protective effect of FA for type 2 diabetes, heart disease, hypertension, stroke, nonalcoholic fatty liver disease, and polycystic ovary syndrome. FA is distinct from UFA by its association with lower liver fat and protection from cardiometabolic diseases; it was not associated with visceral or pancreatic fat. Understanding the difference in FA and UFA may lead to new insights in preventing, predicting, and treating cardiometabolic diseases. | en_GB |
dc.description.sponsorship | Academy of Medical Sciences | en_GB |
dc.description.sponsorship | Diabetes UK | en_GB |
dc.description.sponsorship | Calico Life Sciences LLC | en_GB |
dc.format.extent | 1843-1856 | |
dc.format.medium | Print-Electronic | |
dc.identifier.citation | Vol. 70, No. 8, pp. 1843-1856 | en_GB |
dc.identifier.doi | https://doi.org/10.2337/db21-0129 | |
dc.identifier.grantnumber | SBF004\1079 | en_GB |
dc.identifier.grantnumber | 17/0005594 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/128636 | |
dc.identifier | ORCID: 0000-0001-8746-0947 (Martin, Susan) | |
dc.identifier | ORCID: 0000-0002-9256-6065 (Tyrrell, Jessica) | |
dc.identifier | ORCID: 0000-0003-0750-8248 (Beaumont, Robin N) | |
dc.identifier | ScopusID: 57156164500 (Beaumont, Robin N) | |
dc.identifier | ORCID: 0000-0003-1726-948X (Wood, Andrew R) | |
dc.identifier | ORCID: 0000-0001-9672-9477 (Yaghootkar, Hanieh) | |
dc.language.iso | en | en_GB |
dc.publisher | American Diabetes Association | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/33980691 | en_GB |
dc.rights | © 2021 by the American Diabetes Association | en_GB |
dc.subject | Magnetic resonance imaging | en_GB |
dc.subject | genome-wide association study | en_GB |
dc.subject | cardiometabolic disease | en_GB |
dc.subject | favourable adiposity | en_GB |
dc.subject | ectopic fat | en_GB |
dc.subject | metabolic syndrome | en_GB |
dc.title | Genetic evidence for different adiposity phenotypes and their opposing influences on ectopic fat and risk of cardiometabolic disease. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2022-01-28T13:31:25Z | |
dc.identifier.issn | 0012-1797 | |
exeter.place-of-publication | United States | |
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.eissn | 1939-327X | |
dc.identifier.journal | Diabetes | en_GB |
dc.relation.ispartof | Diabetes, 70(8) | |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dcterms.dateAccepted | 2021-05-06 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2021-05-12 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2022-01-28T13:25:06Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2022-01-28T13:32:05Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2021-05-12 | |