Genome-wide association study of diabetogenic adipose morphology in the GENetics of Adipocyte Lipolysis (GENiAL) Cohort

Lundbäck, V., Kulyté, A., Arner, P., Strawbridge, R. J. and Dahlman, I. (2020) Genome-wide association study of diabetogenic adipose morphology in the GENetics of Adipocyte Lipolysis (GENiAL) Cohort. Cells, 9(5), e1085. (doi: 10.3390/cells9051085)

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Abstract

An increased adipocyte size relative to the size of fat depots, also denoted hypertrophic adipose morphology, is a strong risk factor for the future development of insulin resistance and type 2 diabetes. The regulation of adipose morphology is poorly understood. We set out to identify genetic loci associated with adipose morphology and functionally evaluate candidate genes for impact on adipocyte development. We performed a genome-wide association study (GWAS) in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort comprising 948 participants who have undergone abdominal subcutaneous adipose biopsy with a determination of average adipose volume and morphology. The GWAS identified 31 genetic loci displaying suggestive association with adipose morphology. Functional evaluation of candidate genes by small interfering RNAs (siRNA)-mediated knockdown in adipose-derived precursor cells identified six genes controlling adipocyte renewal and differentiation, and thus of potential importance for adipose hypertrophy. In conclusion, genetic and functional studies implicate a regulatory role for ATL2, ARHGEF10, CYP1B1, TMEM200A, C17orf51, and L3MBTL3 in adipose morphology by their impact on adipogenesis.

Item Type:Articles
Additional Information:Funding: R.J.S. is supported by a the UKRI innovation-HDR-UK Fellowship (MR/S003061/1). I.D. is supported by the Strategic Research Program in Diabetes at Karolinska Institutet (Genetic and long-term epigenetic studies of changes in adipose function), Swedish Research Council (2019-00997), Novo Nordisk foundation (The Role of Adipose Tissue in Cardiovascular Disease), and the Swedish Diabetes Association (DIA2019-407).
Keywords:adipose morphology, adipogenesis, genome-wide association study (GWAS), genetic loci, GENetics of Adipocyte Lipolysis (GENiAL) cohort.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Strawbridge, Dr Rona
Authors: Lundbäck, V., Kulyté, A., Arner, P., Strawbridge, R. J., and Dahlman, I.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
Journal Name:Cells
Publisher:MDPI
ISSN:2073-4409
ISSN (Online):2073-4409
Copyright Holders:Copyright © 2020 by the authors
First Published:First published in Cells 9(5):1085
Publisher Policy:Reproduced under a Creative Commons Licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
302131Understanding the excess risk of cardiometabolic disease in individuals with serious mental illnessJill PellMedical Research Council (MRC)MR/S003061/1HW - Public Health