Genome-wide meta-analysis of brain volume identifies genomic loci and genes shared with intelligence.
Genome-wide meta-analysis of brain volume identifies genomic loci and genes shared with intelligence.
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DOI：
10.1038/s41467-020-19378-5
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发表时间：
2020-11-05
影响因子：
16.6
通讯作者：
Posthuma D
中科院分区：
文献类型：
--
作者：
Jansen PR;Nagel M;Watanabe K;Wei Y;Savage JE;de Leeuw CA;van den Heuvel MP;van der Sluis S;Posthuma D
人类智力和脑容量（BV）之间的表型相关性相当大（r≈0.40），并且已被证明是由于共享的遗传因素。为了进一步研究驱动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，我们进行了大型BV GWAS荟萃分析（N = 47,316个个体），然后进行了功能注释和基因定位。我们鉴定出18个基因组位点（14个以前没有关联），涉及343个基因（270个以前没有关联）和18个BV的生物学途径。其次，我们使用现有的智力GWAS （N = 269,867个个体），估计BV与智力之间的遗传相关（rg）为0.24。我们发现，rg部分可归因于GWAS在5个基因组位点上的物理重叠。我们发现了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项中，我们优先考虑最有可能产生功能影响的32项。这些结果提供了有关细菌性脑膜炎的遗传学信息，并为细菌性脑膜炎与智力共享的遗传病因提供了生物学见解。以前已经发现脑容量和智力具有共同的遗传病因，但尚未确定具体的共同遗传信号。在这里，作者对脑容量进行了全基因组关联研究，找到了驱动脑容量和智力的共同基因位点。
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 (rg) between BV and intelligence to be 0.24. We show that the rg 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. Brain volume and intelligence have been previously found to have shared genetic etiology, but the specific common genetic signals have not been identified. Here, the authors perform a genome-wide association study on brain volume, finding common genetic loci driving brain volume and intelligence.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ