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The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Nat Med. 2025 Jul 21. doi: 10.1038/s41591-025-03827-z.
Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European ancestry. For other populations, this ranged from 16% in East Asian-Americans to 2.2% in rural Ugandans. In the ALSPAC study, children with higher PGSs showed accelerated BMI gain from age 2.5 years to adolescence, with earlier adiposity rebound. Adding the PGS to predictors available at birth nearly doubled explained variance for BMI from age 5 onward (for example, from 11% to 21% at age 8). Up to age 5, adding the PGS to early-life BMI improved prediction of BMI at age 18 (for example, from 22% to 35% at age 5). Higher PGSs were associated with greater adult weight gain. In intensive lifestyle intervention trials, individuals with higher PGSs lost modestly more weight in the first year (0.55 kg per s.d.) but were more likely to regain it. Overall, these data show that PGSs have the potential to improve obesity prediction, particularly when implemented early in life.
体重指数（BMI）的多基因评分（PGS）可能有助于肥胖症的早期预防和针对性治疗。利用来自GIANT联盟和23andMe公司的多达510万人的基因数据（4.6%为非洲血统，14.4%为美洲血统，8.4%为东亚血统，71.1%为欧洲血统，1.5%为南亚血统），我们开发了特定血统和多血统的PGS。多血统评分解释了欧洲血统的英国生物银行参与者中17.6%的BMI变异。对于其他人群，这一比例在东亚裔美国人中为16%，在乌干达农村地区为2.2%。在阿冯纵向父母与儿童发育研究（ALSPAC）中，PGS较高的儿童在2.5岁至青春期期间BMI增长加速，脂肪反弹更早。将PGS添加到出生时可用的预测因素中，从5岁起BMI的解释方差几乎增加了一倍（例如，8岁时从11%增加到21%）。在5岁之前，将PGS添加到早期BMI中可改善对18岁时BMI的预测（例如，5岁时从22%提高到35%）。较高的PGS与更大的成年体重增加有关。在强化生活方式干预试验中，PGS较高的个体在第一年体重减轻略多（每标准差0.55千克），但更有可能反弹。总体而言，这些数据表明PGS有改善肥胖预测的潜力，尤其是在生命早期实施时。
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