How is "Persistent Obesity" encoded by the genome?
Maintaining healthy body weight is important for all of us. Being at a healthy weight can prevent and control many diseases and conditions such as cardiovascular disease, endocrine, and psychiatric diseases. Obesity has been found to be a complex trait that may be impacted by environmental interventions and many genetic variations that could affect obesity prevalence and its persistence over a lifetime.
One of the most important gene families that have been associated with obesity is the peroxisome proliferator-activated receptors family (PPARs). The PPARG gene is known as the most important key regulator of adipogenesis that regulates the transcription of many other genes involved in cellular differentiation and lipid (accumulation. Many association studies that have been conducted have discovered the underlying relation between obesity-related risk factors and SNPs located at PPARG using a single SNP analysis. However, there have been no prior studies that address the correlation between SNPs in association analysis. Using the KMR model (helpful for showing joint effect of SNP), researchers investigated the association between SNPs located at the PPAR gene with long-term persistent obesity.
All adult individuals who had reported BMI data available for at least nine years (three phases) in the Tehran genetic Cardio-metabolic Study (TCGS) were included in this study. Individuals who always had a BMI between 30 and 35 were assigned to the long-term persistent obese study group (n=1,676 mean age 49 years), and individuals who always had a BMI between 20 and 25 over nine years were assigned to the persistent normal weight group (n=1,547, mean age 40 years). At entry time, the two groups had a significant difference between all measured clinical characteristics such as obesity-related factors as well as lipid profiles, with the exception of HDL. This association analysis revealed that a cluster of nine SNPs located upstream of PPARG have a significant joint effect on persistent obesity. One of the SNPs was rs6802898, of which the T allele tended to increase the risk of long-term persistent obesity. To understand the interaction between the SNPs, the number of risk alleles for these nine SNPs (risk score) and mean BMI of all phases for each individual were analyzed. BMI mean (MBM) in individuals with no risk allele is about 27.5, and this value increases in individuals with one or two risk alleles. Furthermore, with a risk score of 5 serving as a separator point to categorize individuals into two groups (risk scoreless and more than five), there is a significant association between persistent obesity and risk score.
This is the first study on the association between PPARG variants with persistent obesity. Three of the nine associated markers were reported in previous GWAS studies to be associated with related diseases. Read more about the study here:
https://pubmed.ncbi.nlm.nih.gov/33389720/
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