Widespread covariation of early environmental exposures and trait-associated polygenic variation
Widespread covariation of early environmental exposures and trait-associated polygenic variation
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DOI：
10.1073/pnas.1707178114
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发表时间：
2017-10-01
影响因子：
11.1
通讯作者：
Plomin, R.
中科院分区：
文献类型：
--
作者：
Krapohl, E.;Hannigan, L. J.;Plomin, R.
虽然基因与环境的相关性已被家族研究和最近的snp遗传力研究所认识和研究，但遗传对性状的影响捕获环境危险因素或保护因素的可能性被多基因预测模型所忽视。我们研究了由全基因组关联研究（GWASs）鉴定的性状相关多基因变异与特定环境暴露之间的共变异，使用基因组相关性矩阵限制最大似然模型控制总体遗传相关性。在一个具有英国代表性的样本（n = 6,710）中，我们发现与后代性状相关的多基因变异与父母行为和与儿童发育结果相关的特征之间存在广泛的共变，而不受种群分层的影响。例如，后代患精神分裂症的遗传风险与父亲的年龄有关（R-2 = 0.002, P = 3e- 04），后代教育相关的变异与母乳喂养（R-2 = 0.021, P = 7e-30）、母亲在怀孕期间吸烟（R-2 = 0.008, P = 5e-13）、父母打孩子（R-2 = 0.01, P = 4e-15）、家庭收入（R-2 = 0.032, P = 1e-22）、看电视（R-2 = 0.034, P = 5e-47）、母亲受教育程度（R-2 = 0.065, P = 3e-96）相关。教育相关的多基因变异还捕获了环境暴露与儿童注意力不集中/多动、行为问题和教育成就之间的共变异。性状GWAS鉴定的遗传变异部分捕获了环境风险因素或保护因素，这一发现对风险预测模型和GWAS研究结果的解释具有直接意义。
Although gene-environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between trait-associated polygenic variation identified by genome-wide association studies (GWASs) and specific environmental exposures, controlling for overall genetic relatedness using a genomic relatedness matrix restricted maximum-likelihood model. In a UK-representative sample (n = 6,710), we find widespread covariation between offspring trait-associated polygenic variation and parental behavior and characteristics relevant to children's developmental outcomes-independently of population stratification. For instance, offspring genetic risk for schizophrenia was associated with paternal age (R-2 = 0.002; P = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding (R-2 = 0.021; P = 7e-30), maternal smoking during pregnancy (R-2 = 0.008; P = 5e-13), parental smacking (R-2 = 0.01; P = 4e-15), household income (R-2 = 0.032; P = 1e-22), watching television (R-2 = 0.034; P = 5e-47), and maternal education (R-2 = 0.065; P = 3e-96). Education-associated polygenic variation also captured covariation between environmental exposures and children's inattention/hyperactivity, conduct problems, and educational achievement. The finding that genetic variation identified by trait GWASs partially captures environmental risk factors or protective factors has direct implications for risk prediction models and the interpretation of GWAS findings.