Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Nat Commun. 2020 Nov 5;11(1):5606. doi: 10.1038/s41467-020-19378-5.
The phenotypic correlation between human intelligence and brain volume (BV) is considerable (r ≈ 0.40), and has been shown to be due to shared genetic factors. To further examine specific genetic factors driving this correlation, we present genomic analyses of the genetic overlap between intelligence and BV using genome-wide association study (GWAS) results. First, we conduct a large BV GWAS meta-analysis (N = 47,316 individuals), followed by functional annotation and gene-mapping. We identify 18 genomic loci (14 not previously associated), implicating 343 genes (270 not previously associated) and 18 biological pathways for BV. Second, we use an existing GWAS for intelligence (N = 269,867 individuals), and estimate the genetic correlation (r) between BV and intelligence to be 0.24. We show that the r is partly attributable to physical overlap of GWAS hits in 5 genomic loci. We identify 92 shared genes between BV and intelligence, which are mainly involved in signaling pathways regulating cell growth. Out of these 92, we prioritize 32 that are most likely to have functional impact. These results provide information on the genetics of BV and provide biological insight into BV's shared genetic etiology with intelligence.
人类智力和脑容量（BV）之间的表型相关性相当大（r≈0.40），并且已经证明这是由于共同的遗传因素。为了进一步研究导致这种相关性的特定遗传因素，我们使用全基因组关联研究（GWAS）结果对智力和 BV 之间的遗传重叠进行了基因组分析。首先，我们进行了大规模的 BV GWAS 荟萃分析（N=47316 人），然后进行功能注释和基因映射。我们确定了 18 个基因组位点（以前未关联的 14 个），涉及 343 个基因（以前未关联的 270 个）和 18 个 BV 生物学途径。其次，我们使用现有的智力 GWAS（N=269867 人），并估计 BV 和智力之间的遗传相关性（r）为 0.24。我们表明，r 部分归因于 5 个基因组位点 GWAS 命中的物理重叠。我们确定了 92 个 BV 和智力之间的共享基因，这些基因主要参与调节细胞生长的信号通路。在这 92 个基因中，我们优先考虑了 32 个最有可能具有功能影响的基因。这些结果提供了关于 BV 遗传学的信息，并为 BV 与智力共享遗传病因学提供了生物学见解。
