Predicting anthropometric and metabolic traits with a genetic risk score for obesity in a sample of Pakistanis

Sobia Rana,Adil Anwar Bhatti

doi:10.1038/s41598-021-87702-0

Abstract

Obesity is an outcome of multiple factors including environmental and genetic influences. Common obesity is a polygenic trait indicating that multiple genetic variants act synergistically to influence its expression. We constructed a genetic risk score (GRS) based on five genetic variants (MC4R rs17782313, BDNF rs6265, FTO rs1421085, TMEM18 rs7561317, and NEGR1 rs2815752) and examined its association with obesity-related traits in a sample of Pakistanis. The study involved 306 overweight/obese (OW/OB) and 300 normal-weight (NW) individuals. The age range of the study participants was 12–63 years. All anthropometric and metabolic parameters were measured for each participant via standard procedures and biochemical assays, respectively. The genetic variants were genotyped by allelic discrimination assays. The age- and gender-adjusted associations between the GRS and obesity-related anthropometric and metabolic measures were determined using linear regression analyses. The results showed that OW/OB individuals had significantly higher mean ranks of GRS than NW individuals. Moreover, a significant association of the GRS with obesity-related anthropometric traits was seen. However, the GRS did not appear to affect any obesity-related metabolic parameter. In conclusion, our findings indicate the combined effect of multiple genetic variants on the obesity-related anthropometric phenotypes in Pakistanis.

Highlights

Obesity is a multifactorial and complex metabolic disorder involving a chronic imbalance of energy homeostasis that has adverse implications for health such as dyslipidemia, arterial hypertension, coronary heart disease, type 2 diabetes mellitus, ovarian polycystosis, gallbladder lithiasis, sleep apnea syndrome, arthropathy, cerebral vasculopathy, and some n eoplasms[1]
The studies for exploring the combined effect of multiple genetic variants on the risk of obesity and related traits regarding Pakistani population are in their infancy
As common obesity has a polygenic inheritance, the assessment of cumulative effect based on genetic risk score (GRS) is very crucial to fully comprehend the components of genetic architecture and physiopathology of obesity

Summary

Introduction

Obesity is a multifactorial and complex metabolic disorder involving a chronic imbalance of energy homeostasis that has adverse implications for health such as dyslipidemia, arterial hypertension, coronary heart disease, type 2 diabetes mellitus, ovarian polycystosis, gallbladder lithiasis, sleep apnea syndrome, arthropathy, cerebral vasculopathy, and some n eoplasms[1]. The current study has been undertaken to compute the GRS based on five obesity-linked key loci including MC4R rs17782313, BDNF rs6265, FTO rs1421085, TMEM18 rs7561317, and NEGR1 rs2815752 in this at-risk and under-represented population.

Results

Conclusion