Could interventions on physical activity mitigate genomic liability for obesity? Applying the health disparity framework in genetically informed studies.
Could interventions on physical activity mitigate genomic liability for obesity? Applying the health disparity framework in genetically informed studies.
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DOI：
10.1007/s10654-023-00980-y
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发表时间：
2023-04
影响因子：
13.6
通讯作者：
De Stavola, Bianca L.
中科院分区：
文献类型：
--
作者：
Herle, Moritz;Pickles, Andrew;Pain, Oliver;Viner, Russell;Pingault, Jean-Baptiste;De Stavola, Bianca L.
多基因评分（PGS）现在通常用于纵向队列研究，导致其整合到流行病学研究中。在这项工作中，我们的目标是探索如何多基因的分数可以被用来作为暴露在因果推理为基础的方法，特别是中介分析。我们建议估计在何种程度上的关联多基因得分索引遗传责任的结果可以减轻潜在的干预调解。为此，我们使用干预差异测量方法，该方法允许我们将暴露对结果的调整后的总效应与我们对潜在可修改的介质进行干预后仍然存在的关联进行比较。作为一个例子，我们分析了来自两个英国队列的数据，千禧年队列研究（MCS，N = 2575）和雅芳家长和儿童纵向研究（ALSPAC，N = 3347）。在这两种情况下，暴露是肥胖的遗传倾向（由BMI的PGS表示），结果是儿童晚期/青少年早期BMI，中介和潜在干预目标是身体活动，在暴露和结果之间进行测量。我们的研究结果表明，对儿童体力活动的潜在干预可以减轻儿童肥胖的遗传倾向。我们建议，包括PGSs在健康差距的措施的方法，和因果推理为基础的方法更广泛，是一个有价值的除了复杂的健康结果的基因-环境相互作用的研究。在线版本包含补充材料，可通过10.1007/s10654-023-00980-y获得。
Polygenic scores (PGS) are now commonly available in longitudinal cohort studies, leading to their integration into epidemiological research. In this work, our aim is to explore how polygenic scores can be used as exposures in causal inference-based methods, specifically mediation analyses. We propose to estimate the extent to which the association of a polygenic score indexing genetic liability to an outcome could be mitigated by a potential intervention on a mediator. To do this this, we use the interventional disparity measure approach, which allows us to compare the adjusted total effect of an exposure on an outcome, with the association that would remain had we intervened on a potentially modifiable mediator. As an example, we analyse data from two UK cohorts, the Millennium Cohort Study (MCS, N = 2575) and the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 3347). In both, the exposure is genetic liability for obesity (indicated by a PGS for BMI), the outcome is late childhood/early adolescent BMI, and the mediator and potential intervention target is physical activity, measured between exposure and outcome. Our results suggest that a potential intervention on child physical activity can mitigate some of the genetic liability for childhood obesity. We propose that including PGSs in a health disparity measure approach, and causal inference-based methods more broadly, is a valuable addition to the study of gene-environment interplay in complex health outcomes. The online version contains supplementary material available at 10.1007/s10654-023-00980-y.
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影响因子：
9.8
作者：
Cobb M
通讯作者：
Cobb M
影响因子：
4.9
作者：
Herle, Moritz;Pickles, Andrew;Micali, Nadia;Abdulkadir, Mohamed;De Stavola, Bianca L.
通讯作者：
De Stavola, Bianca L.
影响因子：
5
作者：
De Stavola BL;Daniel RM;Ploubidis GB;Micali N
通讯作者：
Micali N
DOI：
10.1136/bmj.e4759
发表时间：
2012-09-25
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Friedemann C;Heneghan C;Mahtani K;Thompson M;Perera R;Ward AM
通讯作者：
Ward AM
DOI：
10.1002/ajmg.b.32709
发表时间：
2019-09-01
影响因子：
2.8
作者：
Hubel, Christopher;Gaspar, Helena A.;Breen, Gerome
通讯作者：
Breen, Gerome