MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, United Kingdom;
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, United Kingdom.
Proc Natl Acad Sci U S A. 2017 Oct 31;114(44):11727-11732. doi: 10.1073/pnas.1707178114. Epub 2017 Oct 16.
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 ( = 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 ( = 0.002; = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding ( = 0.021; = 7e-30), maternal smoking during pregnancy ( = 0.008; = 5e-13), parental smacking ( = 0.01; = 4e-15), household income ( = 0.032; = 1e-22), watching television ( = 0.034; = 5e-47), and maternal education ( = 0.065; = 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.
尽管基因-环境相关性已被家系研究和最近的 SNP 遗传力研究所认识和研究，但多基因预测模型忽略了遗传对特征的影响是否能捕捉环境风险因素或保护因素。我们使用基于基因组亲缘关系矩阵的限制最大似然模型，控制了总体遗传相关性，调查了全基因组关联研究（GWAS）鉴定的与特征相关的多基因变异与特定环境暴露之间的共变。在一个具有英国代表性的样本（n = 6710）中，我们发现后代特征相关的多基因变异与与儿童发展结果相关的父母行为和特征之间存在广泛的共变，与人群分层无关。例如，精神分裂症后代的遗传风险与父亲年龄相关（β=0.002；p=1e-04），后代与教育相关的变异与母乳喂养的变异性相关（β=0.021；p=7e-30），母亲在怀孕期间吸烟（β=0.008；p=5e-13），父母打孩子（β=0.01；p=4e-15），家庭收入（β=0.032；p=1e-22），看电视（β=0.034；p=5e-47），和母亲的教育程度（β=0.065；p=3e-96）。与教育相关的多基因变异也捕捉到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。GWAS 鉴定的遗传变异部分捕捉到环境风险因素或保护因素的发现，对风险预测模型和 GWAS 结果的解释具有直接影响。
