Department of Food Science and Nutrition, Keimyung University, Daegu 42601, Republic of Korea.
Nutrients. 2024 Sep 3;16(17):2972. doi: 10.3390/nu16172972.
Our study aimed to identify sweetness preference-associated single-nucleotide polymorphisms (SNPs), characterize the related genetic loci, and develop SNP-based polygenic risk scores (PRS) to analyze their associations with obesity. For genotyping, we utilized a pooled genome-wide association study (GWAS) dataset of 18,499 females and 10,878 males. We conducted genome-wide association analyses, functional annotation, and employed the weighted method to calculate the levels of PRS from 677 sweetness preference-related SNPs. We used Cox proportional hazards modeling with time-varying covariates to estimate age-adjusted and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for obesity incidence. We also tested the correlation between PRS and environmental factors, including smoking and dietary components, on obesity. Our results showed that in males, the TT genotype of rs4861982 significantly increased obesity risk compared to the GG genotype in the Health Professionals Follow-up Study (HPFS) cohort (HR = 1.565; 95% CI, 1.122-2.184; = 0.008) and in the pooled analysis (HR = 1.259; 95% CI, 1.030-1.540; = 0.025). Protein tyrosine phosphatase receptor type O (PTPRO) was identified as strongly associated with sweetness preference, indicating a positive correlation between sweetness preference and obesity risk. Moreover, each 10 pack-year increment in smoking was significantly associated with an increased risk of obesity in the HPFS cohort (HR = 1.024; 95% CI, 1.000-1.048) in males but not in females. In conclusion, significant associations between rs4861982, sweetness preference, and obesity were identified, particularly among males, where environmental factors like smoking are also correlated with obesity risk.
我们的研究旨在确定与甜味偏好相关的单核苷酸多态性（SNP），并对其相关遗传位点进行特征描述，开发基于 SNP 的多基因风险评分（PRS）来分析其与肥胖的关联。我们利用了 18499 名女性和 10878 名男性的汇总全基因组关联研究（GWAS）数据集进行基因分型。我们进行了全基因组关联分析、功能注释，并使用加权方法计算了 677 个与甜味偏好相关的 SNP 的 PRS 水平。我们使用 Cox 比例风险模型和时变协变量来估计肥胖发病率的年龄调整和多变量风险比（HR）和 95%置信区间（CI）。我们还测试了 PRS 与肥胖相关的环境因素（包括吸烟和饮食成分）之间的相关性。结果表明，在男性中，与 rs4861982 的 GG 基因型相比，TT 基因型在健康专业人员随访研究（HPFS）队列（HR=1.565；95%CI，1.122-2.184；P=0.008）和汇总分析（HR=1.259；95%CI，1.030-1.540；P=0.025）中肥胖风险显著增加。蛋白酪氨酸磷酸酶受体型 O（PTPRO）被确定为与甜味偏好强烈相关，表明甜味偏好与肥胖风险之间存在正相关。此外，在 HPFS 队列中，每增加 10 包年吸烟量与男性肥胖风险增加显著相关（HR=1.024；95%CI，1.000-1.048），但在女性中则不然。总之，在男性中，rs4861982、甜味偏好和肥胖之间存在显著关联，而环境因素如吸烟也与肥胖风险相关。
