Polygenic and socioeconomic risk for high body mass index: 69 years of follow-up across life.
Polygenic and socioeconomic risk for high body mass index: 69 years of follow-up across life.
复制标题
高体重指数的多基因和社会经济风险：69年的终身随访。
DOI：
10.1371/journal.pgen.1010233
复制
发表时间：
2022-07
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
遗传对身体质量指数（BMI）的影响似乎在不同的生命中有显着差异，但现有的研究是模棱两可的，并受到生命过程数据缺乏的限制。因此，我们使用了一项出生队列研究来调查婴儿期至老年（2-69岁）高BMI多基因风险的关联差异和解释方差。第二个目的是调查BMI和一个关键的所谓环境决定因素（儿童社会经济地位）之间的关联如何在生活中不同，以及这是否独立和/或倍增遗传影响。数据来自MRC国家健康与发展调查的2677名参与者，在2-69岁的12个时间点测量BMI。我们使用了来自成人和儿童BMI的GWAS的多个多基因指标，并调查了它们与每个年龄段BMI的相关性。对于多基因对较高成人BMI的易感性，效应量（β）和解释方差（R2）的轨迹出现分歧：解释方差在成年早期达到峰值，此后趋于平稳，而绝对效应量在整个成年期增加。对于多基因易感性较高的儿童体重指数，解释的方差是最大的青春期和成年早期，效果大小的绝对值从青春期到成年期稍小。所有多基因指数与BMI的较高变异相关;分位数回归分析显示，BMI分布上端的效应量较大。社会经济学和多基因风险在整个生命中更高的BMI似乎是相加作用的;我们发现很少有相互作用的证据。我们的研究结果强调了多基因和社会经济因素对一生中BMI的可能独立影响。尽管有相当大的关联，但每个人解释的BMI方差在成年后趋于稳定或下降，而BMI方差本身则增加。这表明，在整个生活中，环境对BMI的影响越来越重要。我们试图更好地了解高体重指数（BMI）的多基因和社会经济风险在一生中的差异，使用出生队列随访2至69年的数据。成人BMI的高多基因风险与年龄较大时BMI的绝对差异较大相关，但解释的方差在成年早期达到峰值，此后趋于稳定。对于儿童期高BMI的多基因风险，解释的方差在青春期和成年早期最大;从青春期到成年期的效应量略小。低社会经济地位也与高BMI效应大小在整个生活中增加，但解释方差在成年期趋于稳定。效应量和解释方差之间的差异可能是由于BMI的表型方差在整个生命中增加：BMI方差的增加与效应量的增加相匹配或超过效应量的增加。由于我们的研究抓住了关键的遗传和共享环境对BMI的影响，我们的研究结果表明，机会（“非共享”）环境影响可能对以后的BMI越来越重要。最后，我们发现几乎没有证据表明社会经济地位和多基因指数之间存在相互作用;相反，两者都与BMI独立相关。因此，我们的研究结果强调了环境和遗传因素对整个生命中BMI的重要性。
Genetic influences on body mass index (BMI) appear to markedly differ across life, yet existing research is equivocal and limited by a paucity of life course data. We thus used a birth cohort study to investigate differences in association and explained variance in polygenic risk for high BMI across infancy to old age (2–69 years). A secondary aim was to investigate how the association between BMI and a key purported environmental determinant (childhood socioeconomic position) differed across life, and whether this operated independently and/or multiplicatively of genetic influences. Data were from up to 2677 participants in the MRC National Survey of Health and Development, with measured BMI at 12 timepoints from 2–69 years. We used multiple polygenic indices from GWAS of adult and childhood BMI, and investigated their associations with BMI at each age. For polygenic liability to higher adult BMI, the trajectories of effect size (β) and explained variance (R2) diverged: explained variance peaked in early adulthood and plateaued thereafter, while absolute effect sizes increased throughout adulthood. For polygenic liability to higher childhood BMI, explained variance was largest in adolescence and early adulthood; effect sizes were marginally smaller in absolute terms from adolescence to adulthood. All polygenic indices were related to higher variation in BMI; quantile regression analyses showed that effect sizes were sizably larger at the upper end of the BMI distribution. Socioeconomic and polygenic risk for higher BMI across life appear to operate additively; we found little evidence of interaction. Our findings highlight the likely independent influences of polygenic and socioeconomic factors on BMI across life. Despite sizable associations, the BMI variance explained by each plateaued or declined across adulthood while BMI variance itself increased. This is suggestive of the increasing importance of chance (‘non-shared’) environmental influences on BMI across life. We sought to better understand how polygenic and socioeconomic risk for high body mass index (BMI) differed across life, using data from a birth cohort followed-up from 2 to 69 years. High polygenic risk for adult BMI was associated with greater absolute differences in BMI at older ages, yet the explained variance peaked in early adulthood and plateaued thereafter. For polygenic risk for high childhood BMI, explained variance was largest in adolescence and early adulthood; effect sizes were marginally smaller from adolescence to adulthood. Low socioeconomic position was also associated with high BMI—effect sizes increased across life yet explained variance plateaued across adulthood. The discrepancy between effect sizes and explained variance was likely due to the phenotypic variance in BMI increasing across life: the increase in BMI variance matched or exceeded the increase in effect sizes. Inasmuch as our study captured key genetic and shared environmental influences on BMI, our findings suggest that chance (‘non-shared’) environmental influences may be increasingly important for BMI at later ages. Finally, we found little evidence for interactions between socioeconomic position and polygenic indices; rather, both were independently associated with BMI. Our findings thus highlight the importance of both environmental and genetic factors for BMI across life.
登录
查看更多内容
DOI：
10.1016/s2468-2667(18)30045-8
发表时间：
2018-04
期刊：
The Lancet. Public health
影响因子：
--
作者：
Bann D;Johnson W;Li L;Kuh D;Hardy R
通讯作者：
Hardy R
影响因子：
7.7
作者：
Bann D;Wright L;Cole TJ
通讯作者：
Cole TJ
影响因子：
3.5
作者：
Brandkvist M;Bjørngaard JH;Ødegård RA;Åsvold BO;Smith GD;Brumpton B;Hveem K;Richardson TG;Vie GÅ
通讯作者：
Vie GÅ
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ