Genetic Variation in the Social Environment Contributes to Health and Disease.
Genetic Variation in the Social Environment Contributes to Health and Disease.
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社会环境中的遗传变异有助于健康和疾病。
DOI：
10.1371/journal.pgen.1006498
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发表时间：
2017-01
期刊：
影响因子：
4.5
通讯作者：
Stegle O
中科院分区：
文献类型：
--
作者：
Baud A;Mulligan MK;Casale FP;Ingels JF;Bohl CJ;Callebert J;Launay JM;Krohn J;Legarra A;Williams RW;Stegle O
评估社会环境对健康和疾病的影响具有挑战性。由于社会效应部分取决于社会伙伴的遗传组成，因此可以从一个个体的基因型和另一个个体的表型之间的关联（社会遗传效应，SGE，也称为间接遗传效应）进行研究。我们首次量化了SGE对100多种生物体表型和实验室小鼠全基因组基因表达的贡献。我们发现，笼中配偶（即SGE）的遗传变异有助于与焦虑，伤口愈合，免疫功能和体重相关的有机体和分子测量的变化。社会遗传效应解释了高达29%的表型变异，并且对于一些性状，它们的贡献超过了直接遗传效应（个体的基因型对其自身表型的影响）。重要的是，我们发现忽略SGE会严重影响直接遗传效应（遗传力）的估计。因此，SGE可能是人类群体复杂性状研究中“缺失遗传力”的一个重要来源。总之，我们的研究揭示了社会环境对表型变异的重要贡献，为使用SGE剖析社会效应奠定了基础，并确定了改善直接遗传效应研究的机会。人与人之间的日常互动会以积极和消极的方式影响他们的健康。通常，介导社会效应的机制是未知的，因此目前研究社会效应的方法仅限于一些表型，其中介导机制是先验已知的或怀疑的。在这里，我们建议利用大多数特征是遗传控制的事实来调查社会环境的影响。为此，我们研究了一个个体的基因型与另一个个体的表型之间的关联（社会遗传效应，SGE，也称为间接遗传效应）。重要的是，SGE可以被研究，即使当介导社会环境的影响的特征是未知的。我们首次量化了SGE对100多种生物体表型和实验室小鼠全基因组基因表达的贡献。我们发现，笼友的遗传变异（即SGE）解释了焦虑，伤口愈合，免疫功能和体重的变化高达29%。因此，我们的研究揭示了社会环境的一个意想不到的巨大影响。此外，我们发现，忽略SGE可以严重偏差估计的直接遗传效应（个人的基因型对自身表型的影响），这对复杂性状的遗传基础的研究具有重要意义。
Assessing the impact of the social environment on health and disease is challenging. As social effects are in part determined by the genetic makeup of social partners, they can be studied from associations between genotypes of one individual and phenotype of another (social genetic effects, SGE, also called indirect genetic effects). For the first time we quantified the contribution of SGE to more than 100 organismal phenotypes and genome-wide gene expression measured in laboratory mice. We find that genetic variation in cage mates (i.e. SGE) contributes to variation in organismal and molecular measures related to anxiety, wound healing, immune function, and body weight. Social genetic effects explained up to 29% of phenotypic variance, and for several traits their contribution exceeded that of direct genetic effects (effects of an individual’s genotypes on its own phenotype). Importantly, we show that ignoring SGE can severely bias estimates of direct genetic effects (heritability). Thus SGE may be an important source of “missing heritability” in studies of complex traits in human populations. In summary, our study uncovers an important contribution of the social environment to phenotypic variation, sets the basis for using SGE to dissect social effects, and identifies an opportunity to improve studies of direct genetic effects. Daily interactions between individuals can influence their health both in positive and negative ways. Often the mechanisms mediating social effects are unknown, so current approaches to study social effects are limited to a few phenotypes for which the mediating mechanisms are known a priori or suspected. Here we propose to leverage the fact that most traits are genetically controlled to investigate the influence of the social environment. To do so, we study associations between genotypes of one individual and phenotype of another individual (social genetic effects, SGE, also called indirect genetic effects). Importantly, SGE can be studied even when the traits that mediate the influence of the social environment are not known. For the first time we quantified the contribution of SGE to more than 100 organismal phenotypes and genome-wide gene expression measured in laboratory mice. We find that genetic variation in cage mates (i.e. SGE) explains up to 29% of the variation in anxiety, wound healing, immune function, and body weight. Hence our study uncovers an unexpectedly large influence of the social environment. Additionally, we show that ignoring SGE can severely bias estimates of direct genetic effects (effects of an individual’s genotypes on its own phenotype), which has important implications for the study of the genetic basis of complex traits.