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
File(s)Genome-wide and abdominal MRI-imaging.pdf (256.71 KB)
Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2019-01-01
Date Acceptance
2018-10-12
Citation
Diabetes, 2019, 68 (1), pp.207-219
ISSN
0012-1797
Publisher
American Diabetes Association
Start Page
207
End Page
219
Journal / Book Title
Diabetes
Volume
68
Issue
1
Copyright Statement
© 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/licens.
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/licens.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000453906300020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
BETA-CELL FUNCTION
BODY-MASS INDEX
INSULIN-RESISTANCE
NORMAL-WEIGHT
METABOLICALLY-OBESE
GLYCEMIC TRAITS
ASSOCIATION
LOCI
IDENTIFICATION
METAANALYSIS
Publication Status
Published
OA Location
http://diabetes.diabetesjournals.org/content/68/1/207.full-text.pdf
Date Publish Online
2018-12-20