Polygenic risk score is associated with metabolically unhealthy obesity: A secondary analysis from an energy-restricted intervention (Brazilian Nuts Study)

IF 0.3 Q4 NUTRITION & DIETETICS

CAHIERS DE NUTRITION ET DE DIETETIQUE Pub Date : 2026-08-01 Epub Date: 2026-09-24 DOI:10.1016/j.cnd.2026.08.087

Darlene Larissa de Souza Vilela, Karla Pereira Balbino, Ana Cláudia Pelissari Kravchychyn, Josefina Bressan, Helen Hermana Miranda Hermsdorff

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The study included 92 adults, both sexes, with overweight (BMI 27–29.9kg/m<sup>2</sup>) or obesity (BMI≥30kg/m<sup>2</sup>), increased waist circumference (≥80cm for women and ≥90cm for men), and elevated body fat (>30% for women and >20% for men). Participants were classified as having metabolically healthy obesity (MHO) with≤1 metabolic abnormality and as having metabolically unhealthy obesity (MUO) with≥2 metabolic abnormalities. Metabolic abnormalities included impaired fasting glucose/insulin resistance, dyslipidemia (low HDL cholesterol and/or elevated triglycerides), and hypertension. The PRS was composed of four single-nucleotide polymorphisms (SNPs) (FTO rs9939609; FTO rs1121980; MC4R rs17782313; LEP rs7799039). An unweighted polygenic risk score (dominant model). Defined as the sum of risk alleles, individuals carrying 1 or 2 risk alleles are assigned a value of 1, yielding a PRS ranging from 0 to 4. 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The PRS was composed of four single-nucleotide polymorphisms (SNPs) (FTO rs9939609; FTO rs1121980; MC4R rs17782313; LEP rs7799039). An unweighted polygenic risk score (dominant model). Defined as the sum of risk alleles, individuals carrying 1 or 2 risk alleles are assigned a value of 1, yielding a PRS ranging from 0 to 4. Logistic regression was performed using Stata® 17.</div><div><h3>Results</h3><div>The sample comprised 59.78% women, mean age of 32.90 years, BMI 33.97kg/m<sup>2</sup>, and 55.43% MUO. PRS categories: 5 (5.43%) are zero, 14 (15.22%) are one, 27 (29.35%) are two, 32 (34.7%) are three, 14 (15.22%) are four. A positive gradient was observed for PRS, particularly in PRS categories 2 and 3. In model 2, adjusted for age and sex (M/F), category 2 was also associated with an increased odds of MUO (OR: 5.04; 95% CI: 1.08–23.59). In another adjusted model that included additional income (minimum wage) and body fat (%), individuals in category 3 showed higher odds of MUO (OR: 7.18; 95% CI: 1.24–41.52).</div></div><div>The sample comprised 59.78% women, mean age of 32.90 years, BMI 33.97kg/m<sup>2</sup>, and 55.43% MUO. PRS categories: 5 (5.43%) are zero, 14 (15.22%) are one, 27 (29.35%) are two, 32 (34.7%) are three, 14 (15.22%) are four. A positive gradient was observed for PRS, particularly in PRS categories 2 and 3. In model 2, adjusted for age and sex (M/F), category 2 was also associated with an increased odds of MUO (OR: 5.04; 95% CI: 1.08–23.59). 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引用次数: 0

Abstract

Objective

To evaluate the association between a polygenic risk score (PRS) and metabolic obesity phenotypes in Brazilian adults.

Methods

This secondary cross-sectional analysis utilized baseline data from the “Brazilian Nuts Study” Phase 3, a randomized controlled trial (ReBec registration number RBR8xzkyp2). All volunteers signed the Informed Consent Form (Ethics Committee's opinion No. 4.543.541/CEPH/UFV). The study included 92 adults, both sexes, with overweight (BMI 27–29.9 kg/m²) or obesity (BMI ≥ 30 kg/m²), increased waist circumference (≥ 80 cm for women and ≥ 90 cm for men), and elevated body fat (> 30% for women and > 20% for men). Participants were classified as having metabolically healthy obesity (MHO) with ≤ 1 metabolic abnormality and as having metabolically unhealthy obesity (MUO) with ≥ 2 metabolic abnormalities. Metabolic abnormalities included impaired fasting glucose/insulin resistance, dyslipidemia (low HDL cholesterol and/or elevated triglycerides), and hypertension. The PRS was composed of four single-nucleotide polymorphisms (SNPs) (FTO rs9939609; FTO rs1121980; MC4R rs17782313; LEP rs7799039). An unweighted polygenic risk score (dominant model). Defined as the sum of risk alleles, individuals carrying 1 or 2 risk alleles are assigned a value of 1, yielding a PRS ranging from 0 to 4. Logistic regression was performed using Stata® 17.

Results

The sample comprised 59.78% women, mean age of 32.90 years, BMI 33.97 kg/m², and 55.43% MUO. PRS categories: 5 (5.43%) are zero, 14 (15.22%) are one, 27 (29.35%) are two, 32 (34.7%) are three, 14 (15.22%) are four. A positive gradient was observed for PRS, particularly in PRS categories 2 and 3. In model 2, adjusted for age and sex (M/F), category 2 was also associated with an increased odds of MUO (OR: 5.04; 95% CI: 1.08–23.59). In another adjusted model that included additional income (minimum wage) and body fat (%), individuals in category 3 showed higher odds of MUO (OR: 7.18; 95% CI: 1.24–41.52).

Conclusion

PRS is associated with a higher presence of metabolic disorders in adults with overweight/obesity, reinforcing the importance of nutrition precision in obesity management. Additionally, absence of a linear trend may suggest that multiple genetic variants with modest effects interact with the environment in a nonlinear manner.

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多基因风险评分与代谢不健康肥胖相关：来自能量限制干预的二次分析（巴西坚果研究）

目的评价巴西成年人多基因风险评分（PRS）与代谢性肥胖表型之间的关系。评估巴西成年人多基因风险评分（PRS）与代谢性肥胖表型之间的关系。该二次横断面分析利用了“巴西坚果研究”第3期的基线数据，这是一项随机对照试验（ReBec注册号RBR8xzkyp2）。所有志愿者均签署知情同意书（伦理委员会意见No. 4.543.541/CEPH/UFV）。该研究包括92名超重（BMI 27-29.9 kg/m2）或肥胖（BMI≥30 kg/m2）的男女成年人，腰围增加（女性≥80 cm，男性≥90 cm），体脂升高（女性≥30%，男性≥20%）。参与者被分为代谢健康型肥胖（MHO），代谢异常≤1个；代谢不健康型肥胖（MUO），代谢异常≥2个。代谢异常包括空腹葡萄糖/胰岛素抵抗受损，血脂异常（低HDL胆固醇和/或甘油三酯升高）和高血压。该PRS由4个单核苷酸多态性（FTO rs9939609; FTO rs1121980; MC4R rs17782313; LEP rs7799039）组成。未加权的多基因风险评分（显性模型）。PRS定义为风险等位基因的总和，携带1个或2个风险等位基因的个体被赋予1的值，从而产生从0到4的PRS。采用Stata®17进行Logistic回归。这项二次横断面分析利用了“巴西坚果研究”3期的基线数据，这是一项随机对照试验（ReBec注册号为RBR8xzkyp2）。所有志愿者均签署知情同意书（伦理委员会意见No. 4.543.541/CEPH/UFV）。该研究包括92名超重（BMI 27-29.9 kg/m2）或肥胖（BMI≥30 kg/m2）的男女成年人，腰围增加（女性≥80 cm，男性≥90 cm），体脂升高（女性≥30%，男性≥20%）。参与者被分为代谢健康型肥胖（MHO），代谢异常≤1个；代谢不健康型肥胖（MUO），代谢异常≥2个。代谢异常包括空腹葡萄糖/胰岛素抵抗受损，血脂异常（低HDL胆固醇和/或甘油三酯升高）和高血压。该PRS由4个单核苷酸多态性（FTO rs9939609; FTO rs1121980; MC4R rs17782313; LEP rs7799039）组成。未加权的多基因风险评分（显性模型）。PRS定义为风险等位基因的总和，携带1个或2个风险等位基因的个体被赋予1的值，从而产生从0到4的PRS。采用Stata®17进行Logistic回归。结果女性占59.78%，平均年龄32.90岁，BMI 33.97 kg/m2， MUO占55.43%。PRS分类：5个（5.43%）为0,14个（15.22%）为1,27个（29.35%）为2,32个（34.7%）为3,14个（15.22%）为4在PRS中观察到正梯度，特别是在PRS类别2和3中。在模型2中，调整了年龄和性别（M/F），第2类也与MUO的几率增加相关（OR: 5.04; 95% CI: 1.08-23.59）。在另一个包括额外收入（最低工资）和体脂（%）的调整模型中，类别3的个体显示出更高的MUO几率（OR: 7.18; 95% CI: 1.24-41.52）。样本中女性占59.78%，平均年龄32.90岁，BMI为33.97 kg/m2， MUO为55.43%。PRS分类：5个（5.43%）为0,14个（15.22%）为1,27个（29.35%）为2,32个（34.7%）为3,14个（15.22%）为4在PRS中观察到正梯度，特别是在PRS类别2和3中。在模型2中，调整了年龄和性别（M/F），第2类也与MUO的几率增加相关（OR: 5.04; 95% CI: 1.08-23.59）。在另一个包括额外收入（最低工资）和体脂（%）的调整模型中，类别3的个体显示出更高的MUO几率（OR: 7.18; 95% CI: 1.24-41.52）。结论prs与超重/肥胖成人代谢紊乱的发生率较高相关，强化了营养精准化在肥胖管理中的重要性。此外，缺乏线性趋势可能表明，具有适度影响的多个遗传变异以非线性方式与环境相互作用。在超重/肥胖的成年人中，PRS与代谢紊乱的较高存在相关，这加强了营养精确在肥胖管理中的重要性。此外，缺乏线性趋势可能表明，具有适度影响的多个遗传变异以非线性方式与环境相互作用。

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来源期刊

CAHIERS DE NUTRITION ET DE DIETETIQUE NUTRITION & DIETETICS-

CiteScore

0.60

自引率

33.30%

发文量

审稿时长

65 days

期刊介绍： Les Cahiers de nutrition et de diététique sont le lieu de communication reconnu pour les médecins spécialistes de la nutrition, les diététiciens, les professionnels et les chercheurs de agro-alimentaire, les enseignants et les étudiants. Les Cahiers de nutrition et de diététique abordent les sujets se rapportant à la biologie générale, à la médecine et à la nutrition, aux aliments, aux comportements alimentaires, à la diététique pratique, ainsi que des thèmes variés : activité physique, apports nutritionnels conseillés, dénutrition, alcool, obésité de enfant, aliments à effet santé, plaisir alimentaire, restauration collective, goûters et collations, allergies alimentaires...