Genome-wide association study identifies genetic loci associated with fat cell number and overlap with genetic risk loci for type 2 diabetes

Kulyté, A., Aman, A., Strawbridge, R. J. , Arner, P. and Dahlman, I. A. (2022) Genome-wide association study identifies genetic loci associated with fat cell number and overlap with genetic risk loci for type 2 diabetes. Diabetes, 71(6), pp. 1350-1362. (doi: 10.2337/db21-0804) (PMID:35320353)

[img] Text
267514.pdf - Accepted Version



Interindividual differences in generation of new fat cells determine body fat and type 2 diabetes risk. We utilized the GENiAL cohort, which consists of participants who have undergone abdominal adipose biopsy, to perform a genome-wide association study (GWAS) of fat cell number (n=896). Candidate genes from the genetic study were knocked down by siRNA in human adipose derived stem cells. We report 318 SNPs and 17 genetic loci displaying suggestive (p<1x10-5) association with fat cell number. Two loci pass threshold for GWAS-significance, on chromosome 2 (lead SNP rs149660479-G) and 7 (rs147389390-deletion). We filtered for fat cell number-associated SNPs (p<1.00x10-5) using evidence of genotype-specific expression. Where this was observed we selected genes for follow-up investigation and hereby identified SPATS2L and KCTD18 as regulators of cell proliferation consistent with the genetic data. Furthermore, 30 reported type 2 diabetes-associated SNPs displayed nominal and consistent associations with fat cell number. Functional follow up of candidate genes identified RPL8, HSD17B12 and PEPD displaying effects on cell proliferation consistent with genetic association and gene expression findings. In conclusion findings presented herein identify SPATS2L, KCTD18, RPL8, HSD17B12, and PEPD of potential importance in controlling fat cell numbers (plasticity), the size of body fat and diabetes risk.

Item Type:Articles
Additional Information:RJS is supported by the University of Glasgow Lord Kelvin/Adam Smith Fellowship. ID 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 (NNF200C0063582), and the Swedish Diabetes Association (DIA2019-407).
Glasgow Author(s) Enlighten ID:Aman, Ms Alisha and Strawbridge, Dr Rona
Authors: Kulyté, A., Aman, A., Strawbridge, R. J., Arner, P., and Dahlman, I. A.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
Journal Name:Diabetes
Publisher:American Diabetes Association
ISSN (Online):1939-327X
Published Online:23 March 2022
Copyright Holders:Copyright © 2022 American Diabetes Association
First Published:First published in Diabetes 71(6): 1350-1362
Publisher Policy:Reproduced in accordance with the publisher copyright policy

University Staff: Request a correction | Enlighten Editors: Update this record