The Use of Body Mass Index Polygenic Risk Score (BMI-PRS) in a Paediatric Population With Obesity

IF 2.5 3区医学 Q1 PEDIATRICS

Pediatric Obesity Pub Date : 2026-07-01 DOI:10.1111/ijpo.70132

Julian Gomahr, Wanda Lauth, Lea Süßenbacher, Max Bergauer, Lotte Forer, Julian Eberhardt, Dagmar Schaffler-Schaden, Raphael Reiter, Katharina Mörwald, Patrick Langthaler, Bernhard Iglseder, Bernhard Paulweber, Maria Flamm, Elmar Aigner, Eugen Trinka, Andrea Bito, Tobias Kiesslich, Ludmilla Kedenko, Bernhard Wernly, Daniel Weghuber

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引用次数: 0

Abstract

Introduction

Polygenic risk scores (PRS) stratify obesity risk in population cohorts, but their value within specialised paediatric obesity clinics—where genetic liability may already be saturated—remains unclear.

Methods

We analysed 246 European adolescents with overweight and obesity (mean ± SD age 13.3 ± 2.2 years; 51% female; BMI 31.6 ± 4.1 kg/m²) attending a tertiary clinic in Salzburg, Austria. BMI-PRS based on people with European ancestry (PGS000027) and two cardiometabolic PRS (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR], type 2 diabetes [T2D]) were computed from Axiom-array genotypes. Distributions were compared with a population-based adult cohort from the same region (n = 2044). Associations with BMI, insulin resistance (HOMA-IR ≥ 2.5), alanine aminotransferase (ALT) and oral-glucose-tolerance parameters were examined by linear and logistic regression adjusted for age and sex.

Results

The adolescent cohort showed a right-shifted BMI-PRS distribution; the lowest quintile exceeded the adult mean (p < 0.001). Within the clinic sample, BMI-PRS neither correlated with BMI (r = −0.11; 95% CI −0.23 to 0.02) nor predicted other parameters investigated. PRS for HOMA-IR and T2D showed similarly null associations.

Conclusions

In a genetically enriched clinical cohort, polygenic scores lose discriminatory power, delineating their optimal use for population screening rather than intra-clinic risk stratification. These data underscore the strong hereditary architecture of paediatric obesity and support context-specific application of precision-medicine tools.

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体重指数多基因风险评分（BMI-PRS）在儿科肥胖人群中的应用

多基因风险评分（PRS）在人群队列中对肥胖风险进行分层，但其在专门的儿科肥胖诊所中的价值仍不清楚，因为那里的遗传倾向性可能已经饱和。方法我们分析了246名欧洲超重和肥胖青少年（平均±SD年龄13.3±2.2岁，51%为女性，BMI 31.6±4.1 kg/m2）在奥地利萨尔茨堡的一家三级诊所就诊。根据Axiom-array基因型计算基于欧洲血统（PGS000027）和两种心脏代谢PRS（胰岛素抵抗稳态模型评估[HOMA-IR]， 2型糖尿病[T2D]）的BMI-PRS。将分布与来自同一地区的基于人群的成人队列（n = 2044）进行比较。通过调整年龄和性别的线性和逻辑回归检验BMI、胰岛素抵抗（HOMA-IR≥2.5）、丙氨酸转氨酶（ALT）和口服葡萄糖耐量参数的相关性。结果青少年队列BMI-PRS分布右移；最低的五分位数超过了成人的平均值（p < 0.001）。在临床样本中，BMI- prs与BMI不相关（r = - 0.11; 95% CI - 0.23 ~ 0.02），也不能预测所研究的其他参数。HOMA-IR和T2D的PRS同样显示无关联。结论：在基因丰富的临床队列中，多基因评分失去了歧视性，描绘了其用于人群筛查而不是临床风险分层的最佳用途。这些数据强调了儿童肥胖的强大遗传结构，并支持精准医疗工具的具体应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric Obesity PEDIATRICS-

CiteScore

7.30

自引率

5.30%

发文量

117

审稿时长

6-12 weeks

期刊介绍： Pediatric Obesity is a peer-reviewed, monthly journal devoted to research into obesity during childhood and adolescence. The topic is currently at the centre of intense interest in the scientific community, and is of increasing concern to health policy-makers and the public at large. Pediatric Obesity has established itself as the leading journal for high quality papers in this field, including, but not limited to, the following: Genetic, molecular, biochemical and physiological aspects of obesity – basic, applied and clinical studies relating to mechanisms of the development of obesity throughout the life course and the consequent effects of obesity on health outcomes Metabolic consequences of child and adolescent obesity Epidemiological and population-based studies of child and adolescent overweight and obesity Measurement and diagnostic issues in assessing child and adolescent adiposity, physical activity and nutrition Clinical management of children and adolescents with obesity including studies of treatment and prevention Co-morbidities linked to child and adolescent obesity – mechanisms, assessment, and treatment Life-cycle factors eg familial, intrauterine and developmental aspects of child and adolescent obesity Nutrition security and the "double burden" of obesity and malnutrition Health promotion strategies around the issues of obesity, nutrition and physical activity in children and adolescents Community and public health measures to prevent overweight and obesity in children and adolescents.