Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nat Genet. 2019 Nov;51(11):1637-1644. doi: 10.1038/s41588-019-0516-6. Epub 2019 Nov 1.
Volumetric variations of the human brain are heritable and are associated with many brain-related complex traits. Here we performed genome-wide association studies (GWAS) of 101 brain volumetric phenotypes using the UK Biobank sample including 19,629 participants. GWAS identified 365 independent genetic variants exceeding a significance threshold of 4.9 × 10, adjusted for testing multiple phenotypes. A gene-based association study found 157 associated genes (124 new), and functional gene mapping analysis linked 146 additional genes. Many of the discovered genetic variants and genes have previously been implicated in cognitive and mental health traits. Through genome-wide polygenic-risk-score prediction, more than 6% of the phenotypic variance (P = 3.13 × 10) in four other independent studies could be explained by the UK Biobank GWAS results. In conclusion, our study identifies many new genetic associations at the variant, locus and gene levels and advances our understanding of the pleiotropy and genetic co-architecture between brain volumes and other traits.
人脑的体积变化具有遗传性，并与许多与大脑相关的复杂特征有关。在这里，我们使用 UK Biobank 样本对 101 种脑容量表型进行了全基因组关联研究 (GWAS)，该样本包括 19629 名参与者。GWAS 确定了 365 个独立的遗传变异，这些变异超过了经过多个表型检验调整后的显著性阈值 4.9×10。基于基因的关联研究发现了 157 个相关基因（124 个是新的），功能基因映射分析还关联了 146 个额外的基因。许多已发现的遗传变异和基因以前与认知和心理健康特征有关。通过全基因组多基因风险评分预测，在另外四项独立研究中，UK Biobank GWAS 结果可以解释超过 4%的表型方差（P=3.13×10）。总之，我们的研究在变异、基因座和基因水平上确定了许多新的遗传关联，增进了我们对大脑体积与其他特征之间的多效性和遗传共同结构的理解。
