世界肥胖联合会预计,到2035年,全球超过一半人口将超重或肥胖。然而,生活方式改变、手术和药物治疗等策略并非普遍可用或有效。
通过利用超过五百万人的遗传数据,一个国际研究团队创建了一种名为多基因风险评分(PGS)的测量方法,该评分与成年期肥胖存在可靠关联,并在幼儿期呈现一致且具有指示性的模式。这些发现有助于识别在生命后期有较高遗传风险发展成肥胖的儿童和青少年,他们可能受益于更早开始的针对性预防策略,如生活方式干预。
哥本哈根大学助理教授、发表在Nature Medicine期刊上的该研究主要作者Roelof Smit表示:"该评分之所以如此强大,在于遗传评分与五岁前直至成年期的体重指数之间存在关联的一致性——这个时间点远早于其他风险因素在儿童后期开始影响体重。理论上,在此阶段进行干预可能产生巨大影响。"
预测肥胖的效果是次优方法的两倍
当共同作用时,人类基因组中的细微变异会对健康产生实际影响。目前已识别出数千种增加肥胖风险的遗传变异,例如作用于大脑并影响食欲的变异。PGS就像一个计算器,它综合了一个人所携带的不同风险变异的影响,提供一个总体评分。该PGS能够解释人体体重指数近五分之一(17%)的变异——远高于以往的研究。
为创建这些PGS,科学家们利用了超过五百万人的遗传数据——这是有史以来规模最大、最多样化的遗传数据集——包括来自人体测量学遗传调查(GIANT)联盟和消费级DNA检测公司23andMe的遗传数据。研究人员随后使用包含超过50万人身体和遗传特征的数据集(包括来自"90年代儿童"研究中随时间追踪的BMI数据),测试了他们的新PGS是否与肥胖相关。他们发现,在预测个体患肥胖风险方面,他们的新PGS效果是先前最佳方法的两倍。
布里斯托大学流行病学副教授、本文第二作者Kaitlin Wade博士表示:"肥胖是一个重大的公共卫生问题,其发展涉及遗传、环境、生活方式和行为等诸多因素。这些因素在人的一生中可能各不相同,我们相信其中一些因素起源于儿童期。
"我们很荣幸能为这项关于肥胖遗传结构的卓越且富有洞察力的研究贡献'90年代儿童'研究的数据。我们希望这项工作将有助于在更早的年龄检测出具有高肥胖风险的个体,这可能对未来产生巨大的临床和公共卫生影响。"
遗传并非宿命
研究团队还调查了个体肥胖遗传风险与生活方式减肥干预(如饮食和运动)效果之间的关系。他们发现,具有较高肥胖遗传风险的个体对干预措施反应更明显,但当干预结束时体重反弹也更快。
尽管利用了更广泛人群的基因组,新的PGS仍有其局限性。例如,它在预测具有欧洲血统人群的肥胖方面远优于预测具有非洲血统的人群。这凸显了在更具代表性群体中进行此类工作的必要性。
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Journal Reference:
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