Applicability of Obesity-Related SNPs and Their Effect Size Measures Defined on Populations with European Ancestry for Genetic Risk Estimation among Roma

Abstract

Investigations on the impact of genetic factors on the development of obesity have been limited regarding the Roma population—the largest and most vulnerable ethnic minority in Europe of Asian origin. Genetic variants identified from genetic association studies are primarily from European populations. With that in mind, we investigated the applicability of data on selected obesity-related single nucleotide polymorphisms (SNPs), obtained from the Hungarian general (HG) population of European origin, on the Hungarian Roma (HR) population. Twenty preselected SNPs in susceptible alleles, known to be significantly associated with obesity-related phenotypes, were used to estimate the effect of these SNPs on body mass index (BMI) and waist circumference (WC) in HG (N = 1783) and HR (N = 1225) populations. Single SNP associations were tested using linear and logistic regression models, adjusted for known covariates. Out of 20 SNPs, four located in FTO (rs1121980, rs1558902, rs9939609, and rs9941349) showed strong association with BMI and WC as continuous variables in both samples. Computations based on Adult Treatment Panel III (ATPIII) and the International Diabetes Federation’s (IDF) European and Asian criteria showed rs9941349 in FTO to be associated only with WC among both populations, and two SNPs (rs2867125, rs6548238) in TMEM18 associated with WC only in HG population. A substantial difference (both in direction and effect size) was observed only in the case of rs1801282 in PPARγ on WC as a continuous outcome. Findings suggest that genetic risk scores based on counting SNPs with relatively high effect sizes, defined based on populations with European ancestry, can sufficiently allow estimation of genetic susceptibility for Roma. Further studies are needed to clarify the role of SNP(s) with protective effect(s).