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Genome-wide Association Study Identifies Genetic Loci Associated with Fat Cell Number and Overlap with Genetic Risk Loci For Type 2 Diabetes
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posted on 2022-03-23, 20:58 authored by Agné Kulyté, Alisha Aman, Rona J.Strawbridge, Peter Arner, Ingrid A. DahlmanInterindividual
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.