Rao D C, Sung Yun J, Winkler Thomas W, Schwander Karen, Borecki Ingrid, Cupples L Adrienne, Gauderman W James, Rice Kenneth, Munroe Patricia B, Psaty Bruce M
Circ Cardiovasc Genet. 2017 Jun;10(3). doi: 10.1161/CIRCGENETICS.116.001649.
Several consortia have pursued genome-wide association studies for identifying novel genetic loci for blood pressure, lipids, hypertension, etc. They demonstrated the power of collaborative research through meta-analysis of study-specific results.
The Gene-Lifestyle Interactions Working Group was formed to facilitate the first large, concerted, multiancestry study to systematically evaluate gene-lifestyle interactions. In stage 1, genome-wide interaction analysis is performed in 53 cohorts with a total of 149 684 individuals from multiple ancestries. In stage 2 involving an additional 71 cohorts with 460 791 individuals from multiple ancestries, focused analysis is performed for a subset of the most promising variants from stage 1. In all, the study involves up to 610 475 individuals. Current focus is on cardiovascular traits including blood pressure and lipids, and lifestyle factors including smoking, alcohol, education (as a surrogate for socioeconomic status), physical activity, psychosocial variables, and sleep. The total sample sizes vary among projects because of missing data. Large-scale gene-lifestyle or more generally gene-environment interaction (G×E) meta-analysis studies can be cumbersome and challenging. This article describes the design and some of the approaches pursued in the interaction projects.
The Gene-Lifestyle Interactions Working Group provides an excellent framework for understanding the lifestyle context of genetic effects and to identify novel trait loci through analysis of interactions. An important and novel feature of our study is that the gene-lifestyle interaction (G×E) results may improve our knowledge about the underlying mechanisms for novel and already known trait loci.
多个联盟开展了全基因组关联研究，以确定血压、血脂、高血压等方面的新基因位点。他们通过对各研究结果的荟萃分析展示了合作研究的力量。
基因-生活方式相互作用工作组成立，旨在推动首次大规模、协同的多血统研究，以系统评估基因-生活方式的相互作用。在第一阶段，对来自多个血统的共149684名个体的53个队列进行全基因组相互作用分析。在第二阶段，纳入另外71个队列中的460791名来自多个血统的个体，对第一阶段中最有前景的一组变异进行重点分析。该研究总共涉及多达610475名个体。目前的重点是心血管特征，包括血压和血脂，以及生活方式因素，包括吸烟、饮酒、教育程度（作为社会经济地位的替代指标）、身体活动、心理社会变量和睡眠。由于数据缺失，各项目的样本总量有所不同。大规模的基因-生活方式或更广泛的基因-环境相互作用（G×E）荟萃分析研究可能既繁琐又具有挑战性。本文介绍了相互作用项目的设计及所采用的一些方法。
基因-生活方式相互作用工作组为理解遗传效应的生活方式背景以及通过相互作用分析识别新的性状位点提供了一个出色的框架。我们研究的一个重要且新颖的特点是，基因-生活方式相互作用（G×E）结果可能会增进我们对新的和已知性状位点潜在机制的了解。
