Validação da associação da variante rs114066381 (de origem africana e potencialmente reguladora) com obesidade em mulheres

Abstract

Obesity is a multifactorial disease with high national and global prevalence and there is an increase in cases in recent decades. BMI (Body Mass Index) is one of the most used ways to classify individuals and identify cases of the disease (BMI>30kg/m2) (WHO, 2000a), despite its limitations. In the context of mixed populations, such as Brazil, the admixture mapping technique is a promising alternative for identifying new genetic variants related to complex phenotypes, such as obesity, in comparison to traditional association studies. In this circumstance, Scliar et al. (2021) identified the rs114066381G>A variant positively associated with BMI in women of African ancestry. As this result was obtained from imputed data, which presents a degree of inherent uncertainty, this work aimed to evaluate the association of rs114066381 with BMI based on genotyping of women with obesity and undergoing treatment at the Hospital das Clínicas of the Federal University of Minas Gerais and at Hospital Santa Casa Belo Horizonte. The EPIGEN Bambuí and Pelotas cohorts, analyzed in Scliar et al. (2021), were used for comparison. Using Fisher's exact association test, we replicated the results of Scliar et al. (2021) using both the Pelotas cohort and the two cohorts in conjunction as a control with respective significant OR values (Odds Ratio) of 4.07 and 3.73. It was not possible to replicate the association in the Bambuí cohort, possibly due to a low sample size. Thus, the rs114066381 variant could be a new variant strongly related to obesity, requiring future functional studies that could reveal its possible functional mechanism.