Department of Biotechnology, College of Science, University of Tehran, Enghelab Avenue, Tehran, 14155-6455, Iran.
Dr. Zeinali's Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran.
Mol Genet Genomics. 2022 Nov;297(6):1495-1503. doi: 10.1007/s00438-022-01923-0. Epub 2022 Aug 10.
Obesity is a major public health issue resulting from an interaction between genetic and environmental factors. Genetic risk scores (GRSs) are useful to summarize the effects of many genetic variants on obesity risk. In this study, we aimed to assess the association of previously well-studied genetic variants with obesity and develop a genetic risk score to anticipate the risk of obesity development in the Iranian population. Among 968 participants, 599 (61.88%) were obese, and 369 (38.12%) were considered control samples. After genotyping, an initial screening of 16 variants associated with body mass index (BMI) was performed utilizing a general linear model (p < 0.25), and seven genetic variants were selected. The association of these variants with obesity was examined using a multivariate logistic regression model (p < 0.05), and finally, five variants were found to be significantly associated with obesity. Two gene score models (weighted and unweighted), including these five loci, were constructed. To compare the discriminative power of the models, the area under the curve was calculated using tenfold internal cross-validation. Among the studied variants, ADRB3 rs4994, FTO rs9939609, ADRB2 rs1042714, IL6 rs1800795, and MTHFR rs1801133 polymorphisms were significantly associated with obesity in the Iranian population. Both of the constructed models were significantly associated with BMI (p < 0.05) and the area under the mean curve of the weighted GRS and unweighted GRS were 70.22% ± 0.05 and 70.19% ± 0.05, respectively. Both GRSs proved to predict obesity and could potentially be utilized as genetic tools to assess the obesity predisposition in the Iranian population. Also, among the studied variants, ADRB3 rs4994 and FTO rs9939609 polymorphisms have the highest impacts on the risk of obesity.
肥胖是由遗传和环境因素相互作用引起的一个主要公共卫生问题。遗传风险评分（GRS）可用于总结许多遗传变异对肥胖风险的影响。本研究旨在评估先前研究充分的遗传变异与肥胖的相关性，并在伊朗人群中开发一种遗传风险评分来预测肥胖发展的风险。在 968 名参与者中，599 名（61.88%）为肥胖者，369 名（38.12%）为对照样本。基因分型后，我们利用一般线性模型（p<0.25）对与体重指数（BMI）相关的 16 个变体进行了初步筛选，并选择了 7 个遗传变体。利用多变量逻辑回归模型（p<0.05）研究这些变体与肥胖的相关性，最终发现 5 个变体与肥胖显著相关。构建了包含这 5 个基因座的两个基因评分模型（加权和非加权）。为了比较模型的判别能力，我们利用十折内部交叉验证计算了曲线下面积。在所研究的变体中，ADRB3 rs4994、FTO rs9939609、ADRB2 rs1042714、IL6 rs1800795 和 MTHFR rs1801133 多态性与伊朗人群的肥胖显著相关。构建的两种模型与 BMI 显著相关（p<0.05），加权 GRS 和非加权 GRS 的平均曲线下面积分别为 70.22%±0.05 和 70.19%±0.05。两种 GRS 均证明可预测肥胖，并且可能被用作遗传工具来评估伊朗人群的肥胖易感性。此外，在所研究的变体中，ADRB3 rs4994 和 FTO rs9939609 多态性对肥胖风险的影响最大。
