Investigating Gene-Gene and Gene-Environment Interactions in the Association Between Overnutrition and Obesity-Related Phenotypes

Introduction – Animal studies suggested that NFKB1, SOCS3 and IKBKB genes could be involved in the association between overnutrition and obesity. This study aims to investigate interactions involving these genes and nutrition affecting obesity-related phenotypes.\ud Methods – We used multifactor dimensionality reduction (MDR) and penalized logistic regression (PLR) to better detect gene/environment interactions in data from the Toronto Nutrigenomics and Health Study (n=1639) using dichotomized body mass index (BMI) and waist circumference (WC) as obesity-related phenotypes. Exposure variables included genotypes on 54 single nucleotide polymorphisms, dietary factors and ethnicity.\ud Results – MDR identified interactions between SOCS3 rs6501199 and rs4969172, and IKBKB rs3747811 affecting BMI in whites; SOCS3 rs6501199 and NFKB1 rs1609798 affecting WC in whites; and SOCS3 rs4436839 and IKBKB rs3747811 affecting WC in South Asians. PLR found a main effect of SOCS3 rs12944581 on BMI among South Asians. \ud Conclusion – MDR and PLR gave different results, but support some results from previous studies