Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction
Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction
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DOI：
10.1038/s41588-020-00754-2
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发表时间：
2021-01-01
期刊：
影响因子：
30.8
通讯作者：
Nivard, Michel G.
中科院分区：
文献类型：
--
作者：
Demange, Perline A.;Malanchini, Margherita;Nivard, Michel G.
受教育程度和认知测试表现的全基因组关联数据的基因组结构方程模型用于估计独立于认知能力的受教育程度变异的遗传成分。研究发现，非认知技能占受教育程度遗传变异的57%。除了认知能力，我们对影响受教育程度的基因结构知之甚少。我们使用基因组结构方程模型和先前的全基因组关联研究（GWASs）对受教育程度（n = 1,131,881）和认知测试表现（n = 257,841）进行研究，以估计SNP与受教育程度差异的关联，该差异与认知能力无关。我们确定了157个全基因组显著位点和一个多基因结构，占受教育程度遗传变异的57%。非认知基因在与认知表现相同的脑组织和细胞类型中富集，但与灰质脑容量的关联不同。非认知遗传学与人格特征、低风险行为和某些精神疾病风险增加有关，从而进一步区分开来。对于社会经济上的成功和长寿，非认知和认知表现遗传学显示出了类似程度的关联。通过对未直接测量的表型进行GWAS，我们提供了影响教育成功的非认知技能的遗传结构的观点。
Genomic structural equation modeling of genome-wide association data for educational attainment and cognitive test performance is used to estimate the genetic component of variation in educational attainment that is independent of cognitive ability. The study finds that noncognitive skills account for 57% of genetic variation in educational attainment.Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used genomic structural equation modeling and prior genome-wide association studies (GWASs) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability. We identified 157 genome-wide-significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Noncognitive genetics were enriched in the same brain tissues and cell types as cognitive performance, but showed different associations with gray-matter brain volumes. Noncognitive genetics were further distinguished by associations with personality traits, less risky behavior and increased risk for certain psychiatric disorders. For socioeconomic success and longevity, noncognitive and cognitive-performance genetics demonstrated associations of similar magnitude. By conducting a GWAS of a phenotype that was not directly measured, we offer a view of genetic architecture of noncognitive skills influencing educational success.