Abstract
Obese Asians are more susceptible to metabolic diseases than obese Caucasians of the same body mass index (BMI). We hypothesized that the genetic variants associated with obesity risk interact with the lifestyles of middle-aged and elderly adults, possibly allowing the development of personalized interventions based on genotype. We aimed to examine this hypothesis in a large city hospital-based cohort in Korea. The participants with cancers, thyroid diseases, chronic kidney disease, or brain-related diseases were excluded. The participants were divided into case and control according to their BMI: ≥25 kg/m2 (case; n = 17,545) and <25 kg/m2 (control; n = 36,283). The genetic variants that affected obesity risk were selected using a genome-wide association study, and the genetic variants that interacted with each other were identified by generalized multifactor dimensionality reduction analysis. The selected genetic variants were confirmed in the Ansan/Ansung cohort, and polygenetic risk scores (PRS)−nutrient interactions for obesity risk were determined. A high BMI was associated with a high-fat mass (odds ratio (OR) = 20.71) and a high skeletal muscle-mass index (OR = 3.38). A high BMI was positively related to metabolic syndrome and its components, including lipid profiles, whereas the initial menstruation age was inversely associated with a high BMI (OR = 0.78). The best model with 5-SNPs included SEC16B_rs543874, DNAJC27_rs713586, BDNF_rs6265, MC4R_rs6567160, and GIPR_rs1444988703. The high PRS with the 5-SNP model was positively associated with an obesity risk of 1.629 (1.475–1.798) after adjusting for the covariates. The 5-SNP model interacted with the initial menstruation age, fried foods, and plant-based diet for BMI risk. The participants with a high PRS also had a higher obesity risk when combined with early menarche, low plant-based diet, and a high fried-food intake than in participants with late menarche, high plant-based diet, and low fried-food intake. In conclusion, people with a high PRS and earlier menarche age are recommended to consume fewer fried foods and a more plant-based diet to decrease obesity risk. This result can be applied to personalized nutrition for preventing obesity.
Highlights
This article is an open access articleAsians with a high body mass index (BMI) have a higher body fat mass than Caucasians
Fat mass and obesity-associated protein (FTO), melanocortin 4 receptor (MC4R), and brain-derived neurotrophic factor (BDNF) genetic variants have been reported to be strongly associated with obesity risk in a genome-wide association study (GWAS) and meta-analysis studies of children and adults of different ethnicities including Europeans, Americans, Asians, and Africans [8,9,10,11,12]
The results show that BMI showed an increasing trend with Polygenetic risk scores (PRS), and the participants with PRS scores of 8 and 9 had a sharp increment in BMI (Figure 2A)
Summary
This article is an open access articleAsians with a high body mass index (BMI) have a higher body fat mass than Caucasians. Most studies have explored the effect of an individual genetic variant on obesity risk [4,5,6,7]. A polygenic model provides the cumulative genetic impact on obesity risk compared to individual genetic variants when the selected genes have gene−gene and SNP−SNP interactions with the pathways of biological relevance to obesity [8]. Fat mass and obesity-associated protein (FTO), melanocortin 4 receptor (MC4R), and brain-derived neurotrophic factor (BDNF) genetic variants have been reported to be strongly associated with obesity risk in a genome-wide association study (GWAS) and meta-analysis studies of children and adults of different ethnicities including Europeans, Americans, Asians, and Africans [8,9,10,11,12]
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