多基因风险评分可预测肥胖风险
|
摘要
<正>肥胖(obesity)是21世纪面临的最严重的健康挑战之一。其中严重肥胖(BMI≥40 kg/m2)问题不仅已影响8%成年美国人的身体健康,而且随着全球经济的发展,在发展中大国(如中国和印度)中等收入人群中也迅速蔓延。最近三十年严重肥胖人数增加了100倍以上[1]。虽然肥胖和各种不健康的生活方式有直接关系,但研究表明肥胖是可以多基因遗传的,内生的DNA变异使得一些人群易感肥胖,而另外一些个体则具有肥胖的"天然"抗性[2]。对于多基因决定的遗传性状,虽然研究人员使用全基因组关联分析(genome-wide association study, GWAS)对这些与表型有关的基因变异位点进行关联性分析,但很多有贡献的变异位点却因阀值过低而被过滤掉,且一些变异位点对表型性状的解释度过低而缺乏临床使用性。多基因风险评分(polygenic risk score)是一种通过GWAS统计数据的基因型效应值来计算评估个体患某种疾病风险的方法 ,近些年来
引文
[1]Collaboration NCDRP, Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016:a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults[J]. Lancet,2017, 390(10113):2627-2642.
[2]YANG J,Bakshi A,Zhu ZH, et al. Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index[J]. Nature Genetics, 2015,47(10):1114.
[3]KHERA AV, CHAFFIN M, ARAGAM KG, et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations[J]. Nature genetics, 2018, 50(9):1219.
[4]LOTTA LA, MOKROSINSKI J, DE OLIVEIRA EM, et al. Human gain-of-function MC4R variants show signaling bias and protect against obesity[J]. Cell, 2019,177(3):597-607. e9.
[5]MEGA JL, STITZIEL NO, SMITH JG, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy:an analysis of primary and secondary prevention trials[J]. The Lancet, 2015, 385(9984):2264-2271.
[2]YANG J,Bakshi A,Zhu ZH, et al. Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index[J]. Nature Genetics, 2015,47(10):1114.
[3]KHERA AV, CHAFFIN M, ARAGAM KG, et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations[J]. Nature genetics, 2018, 50(9):1219.
[4]LOTTA LA, MOKROSINSKI J, DE OLIVEIRA EM, et al. Human gain-of-function MC4R variants show signaling bias and protect against obesity[J]. Cell, 2019,177(3):597-607. e9.
[5]MEGA JL, STITZIEL NO, SMITH JG, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy:an analysis of primary and secondary prevention trials[J]. The Lancet, 2015, 385(9984):2264-2271.