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Ji, Y.* ; Yiorkas, A.M.* ; Frau, F.* ; Mook-Kanamori, D.O.* ; Staiger, H. ; Thomas, E.L.* ; Atabaki-Pasdar, N.* ; Campbell, A.* ; Tyrrell, J.* ; Jones, S.E.* ; Beaumont, R.N.* ; Wood, A.R.* ; Tuke, M.A.* ; Ruth, K.S.* ; Mahajan, A.* ; Murray, A.* ; Freathy, R.M.* ; Weedon, M.N.* ; Hattersley, A.T.* ; Hayward, C.* ; Machann, J. ; Häring, H.-U. ; Franks, P.* ; de Mutsert, R.* ; Pearson, E.* ; Stefan, N. ; Frayling, T.M.* ; Allebrandt, K.V.* ; Bell, J.D.* ; Blakemore, A.I.* ; Yaghootkar, H.*

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.

Diabetes 68, 207-219 (2019)
Verlagsversion Forschungsdaten DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Beta-cell Function; Body-mass Index; Insulin-resistance; Normal-weight; Metabolically-obese; Glycemic Traits; Association; Loci; Identification; Metaanalysis
Sprache
Veröffentlichungsjahr 2019
Prepublished im Jahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Zeitschrift Diabetes
Quellenangaben Band: 68, Heft: 1, Seiten: 207-219 Artikelnummer: , Supplement: ,
Verlag American Diabetes Association
Verlagsort Alexandria, VA.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502400-001
G-502400-002
DOI 10.2337/db18-0708
WOS ID WOS:000453906300020
Scopus ID 85058904141
PubMed ID 30352878
Erfassungsdatum 2018-12-31
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