大规模的外体序列分析确定了肥胖的性别和年龄特异性决定因素
Lena R Kaisinger1, Katherine A Kentistou1, Stasa Stankovic1
1MRC Epidemiology Unit, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK.
Cell genomics
|August 21, 2023
概括
罕见的遗传变异显著影响人体质量指数 (BMI),特定的基因被确定为女性和男性. 这些发现表明,对肥胖的敏感性涉及神经元死亡和DNA损伤.
科学领域:
- 遗传学 是一个遗传学.
- 肥胖问题研究研究
- 人体生理学 人体生理学
背景情况:
- 肥胖是一个主要的全球健康问题,具有强烈的遗传影响.
- 之前的研究发现了影响成年人体重指数 (BMI) 的罕见基因变异.
研究的目的:
- 在一个大型的英国生物银行队列中进行性别分层遗传关联分析.
- 确定影响成人BMI和儿童肥胖的新基因.
主要方法:
- 利用英国生物库数据 (N≈420,000) 进行性别特异性外基因组测序关联分析.
- 研究了罕见的异合体功能丧失变体及其对BMI的影响.
- 分析了与回忆起童年肥胖症相关的罕见变体.
主要成果:
- 鉴定了基因 (DIDO1,PTPRG,SLC12A5),其中罕见的变异会增加女性的BMI.
- 鉴定了罕见变异增加男性BMI的基因 (SLTM),影响大小高达8kg/m2.
- 在OBSCN和MADD中的罕见变异与儿童肥胖症有关.
结论:
- 罕见的遗传变异在肥胖易感性中起着重要作用,具有性别特异性的影响.
- 表明神经元死亡,细胞亡和DNA损伤反应在整个生命周期的肥胖中都与此有关.
- 强调在遗传肥胖研究中需要考虑性别和生命过程.
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