Body fat and type 2 diabetes risk are determined by interindividual changes in creating new fat cells. For a study, researchers conducted a genome-wide association study (GWAS) of fat cell numbers (n=896) in the GENetics of Adipocyte Lipolysis (GENiAL) cohort, which included patients who have undergone abdominal adipose biopsy. In human adipose-derived stem cells, candidate genes from the genetic analysis were knocked down by siRNA. 

They discovered 318 single nucleotide polymorphisms (SNPs) and 17 genetic loci with a possible (P<1 × 10−5) link with fat cell number. Two loci on chromosomes 2 (lead SNP rs149660479-G) and 7 satisfy the GWAS significance level (rs147389390-deletion). Using evidence of genotype-specific expression, they screened for fat cell number–associated SNPs (P< 1.00 × 10−5). Where this was found, they chose genes for further analysis and discovered SPATS2L and KCTD18 as cell proliferation regulators compatible with the genetic evidence. 

Furthermore, 30 SNPs related to type 2 diabetes were shown to have minimal and consistent correlations with fat cell numbers. In addition, in functional analysis of potential genes, RPL8HSD17B12, and PEPD were shown to impact cell proliferation compatible with the genetic association and gene expression data. Finally, the data suggested that SPATS2LKCTD18, RPL8HSD17B12, and PEPD may be necessary for modulating fat cell numbers (plasticity) and body fat size, and diabetes risk.

Reference:diabetesjournals.org/diabetes/article/71/6/1350/144852/Genome-Wide-Association-Study-Identifies-Genetic

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