Genetic risk score predicts risk for overweight and obesity in Finnish preadolescents

Abstract

Summary Common genetic variants predispose to obesity with varying contribution by age. We incorporated known genetic variants into genetic risk scores (GRSs) and investigated their associations with overweight/obesity and central obesity in preadolescents. Furthermore, we compared GRSs with lifestyle factors, and tested if they predict the change in body size and shape in a 4‐year follow‐up. We utilized 1142 subjects from the Finnish Health in Teens (Fin‐HIT) cohort. Overweight and obesity were defined with age‐ and gender‐specific body mass index (BMI) z‐score (BMIz), while central obesity by the waist‐to‐height ratio (WHtR). Background data on parental language, eating habits, leisure‐time physical activity (LTPA) and sleep duration were included. Genotyping was performed with the Metabochip platform. Weighted, standardized GRSs were derived. Of the11‐year‐old children, 25.5% were at least overweight and 90.8% had Finnish speaking background. BMI‐GRS was associated with higher risk for overweight with odds ratio (95% confidence interval) of 1.39 (1.20; 1.60) and obesity 1.41 (1.08; 1.83), but not with central obesity. BMI‐GRS was weakly and inversely associated with the changes in BMIz and WHtR in the 4‐year follow‐up. Waist‐to‐hip ratio‐GRS was not related to any obesity measures at baseline nor in the follow‐up. The effect of BMI‐GRS is similar to that of low LTPA on overweight. An interaction between parental language and BMI‐GRS was noted (P = .019): BMI‐GRS associated more strongly with overweight in Swedish than in Finnish speakers. We further identified two suggestive genetic variants near LOC101926977 and LOC105369677 associated with BMIz in preadolescents which were replicated in the adult population. In preadolescents, known genetic predisposing factors induce a risk for overweight comparable to low LTPA. However, the GRS was poor in predicting short‐term changes in BMI or WHtR.

Ranking of a wide multidomain set of predictor variables of children obesity by machine learning variable importance techniques

“…Prot (%TEI) is followed by the genetic risk score ( GRS ), that supports the genetic component of the BMI in children. This variable aggregates several genetic single nucleotide polymorphisms well described to affect childhood obesity, and has been used previously in studies of pediatric based-populations 35 , 36 . GRSs have been a great success in the study on polygenic diseases, and it could be seen as a personalized risk management strategy for obesity and overweight.…”

Development of a Genetic Risk Score to predict the risk of overweight and obesity in European adolescents from the HELENA study

“…There are few previous studies focusing on BMI-specific GRSs with overweight and obesity in European pediatric populations and none exclusively in European adolescents, which reinforces the potential of our GRS analysis. In a cohort of 1142 Finnish preadolescents, Viljakainen et al 22 constructed a wGRS to predict the risk of overweight (1.39-fold increased odds) and obesity (1.41-fold increased odds) using 30 BMI-related SNPs, stating that their GRS was poor in predicting short-term longitudinal changes in BMI. In two Finnish children and adolescent cohorts, Seyednasrollah et al 21 developed two wGRS of 97 and 19 SNPs previously related to the risk of obesity, and obtained a lightly better prediction accuracy with the 19-SNP GRS than in our study (AUC = 0.769 vs. 0.734).…”

“…This allowed the researchers to use a large database with relevant and diverse information from different populations across Europe. Additionally, only few GRSs to predict the overweight and obesity risk have been developed particularly in European adolescents, an understudied population from the early treatment and prevention perspective 21 , 22 . Similarly to Viljakainen et al 22 , the proposed genetic score of predisposition to obesity defined in this study might efficiently contribute to discern population at risk for overweight and obesity and not just obesity alone.…”

“…Within European populations, Seyednasrollah et al 21 computed two weighted GRS (wGRS) of 97 and 19 SNPs previously related to the risk of obesity in two cohorts including 2262 Finnish children and adolescents (3–18 years). Further, Viljakainen et al 22 developed a wGRS to predict the risk of overweight and obesity in a cohort of 1142 Finnish preadolescents (11.3 ± 0.2 years) considering body mass index (BMI) and 30 BMI-related SNPs from previous genome-wide association studies (GWAS). As only few studies testing obesity risk in European adolescents with GRSs have been conducted, the aim of the present study was to develop a GRS for overweight and obesity in adolescents participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study.…”

Interaction Effect of the Mediterranean Diet and an Obesity Genetic Risk Score on Adiposity and Metabolic Syndrome in Adolescents: The HELENA Study

“…That is the case of genetic risk scores (GRS), that combine a number of single nucleotide polymorphisms (SNPs) by summing the number of risk alleles [ 15 ]. In order to try to prevent the development of obesity and MetS in European adolescents it is crucial to improve our understanding of the predisposing genetic factors [ 16 , 17 ].…”