Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan, South Korea.
Nutr Bull. 2022 Sep;47(3):307-321. doi: 10.1111/nbu.12569. Epub 2022 Jul 15.
We examined the hypothesis that the genetic variants associated with abdominal obesity (AO) risk, excluding skeletal muscle mass impact, interact with lifestyle characteristics of adults aged >40 years in three cohorts from the Korean Genome and Epidemiology Study. Participants from a large city hospital-based cohort, excluding those with cancers, thyroid diseases, chronic kidney disease or brain-related diseases, were divided into AO (case; n = 17 545) and control (n = 36 283) using the cut-offs for waist circumference of 90 cm for men and 85 cm for women. The genetic variants affecting AO risk were chosen from a genome-wide association study in this cohort with obesity-related covariates, including and excluding skeletal muscle mass as a covariate. The genetic variants were confirmed in the other two cohorts. The interaction between the genetic variants was identified by generalised multifactor dimensionality reduction analysis (GMDR). The polygenic risk scores (PRS)-nutrient interactions were determined. Abdominal obesity was associated with SEC16B_rs543874, KCNQ5_rs2796052, CDKAL1_rs9356744, BDNF_rs6265, FTO_rs1421085, MC4R_rs17782313 and GIPR_rs1444988703 adjusting for covariates excluding LBM. However, the best model with 5 single nucleotide polymorphisms (SNP) contained COL3A1_rs3106801, ADAMTS3_rs13105983, KCNQ5_rs2796044, ZFHX3_rs9938769 and MIR17HG_rs7318578 from GMDR when including LBM in covariates. These genetic variants were specific for AO risk. The expression quantitative trait locus (eQTL) analysis showed that the SNP effects were associated with the corresponding gene expression. The high PRS with the 5 SNP model was positively associated with an increased risk of AO of 1.639 (1.463-1.836). The PRS interacted with the age of menarche, energy intake and physical activity. In conclusion, adults with a high PRS, particularly those experiencing early menarche, may particularly benefit from not exceeding energy requirements and from regular physical exercise in order to prevent abdominal obesity. This finding can be applied to personalised nutrition advice to prevent abdominal obesity.
我们检验了这样一个假设，即除了骨骼肌质量的影响外，与腹部肥胖（AO）风险相关的遗传变异与年龄>40 岁的成年人的生活方式特征相互作用，这是在韩国基因组和流行病学研究中的三个队列中进行的。从一个大型城市医院队列中选择参与者，排除患有癌症、甲状腺疾病、慢性肾脏疾病或与大脑相关疾病的患者，根据男性腰围>90cm 和女性腰围>85cm 的标准，将其分为 AO（病例；n=17545）和对照组（n=36283）。在包含肥胖相关协变量（包括和不包括骨骼肌质量作为协变量）的该队列中，从全基因组关联研究中选择影响 AO 风险的遗传变异。在其他两个队列中验证了遗传变异。通过广义多因素维度缩减分析（GMDR）确定遗传变异的相互作用。确定多基因风险评分（PRS）-营养素相互作用。在调整协变量（不包括 LBM）后，AO 与 SEC16B_rs543874、KCNQ5_rs2796052、CDKAL1_rs9356744、BDNF_rs6265、FTO_rs1421085、MC4R_rs17782313 和 GIPR_rs1444988703 相关。然而，当包含 LBM 作为协变量时，最佳模型包含来自 GMDR 的 5 个单核苷酸多态性（SNP），即 COL3A1_rs3106801、ADAMTS3_rs13105983、KCNQ5_rs2796044、ZFHX3_rs9938769 和 MIR17HG_rs7318578。这些遗传变异是 AO 风险的特异性因素。表达数量性状基因座（eQTL）分析表明，SNP 效应与相应基因的表达相关。高 PRS 与 5 SNP 模型呈正相关，AO 风险增加 1.639（1.463-1.836）。PRS 与初潮年龄、能量摄入和体力活动相互作用。总之，高 PRS 的成年人，特别是那些初潮较早的成年人，为了预防腹部肥胖，可能特别受益于不超过能量需求和定期进行体育锻炼。这一发现可应用于个性化营养建议，以预防腹部肥胖。
