Sniekers Suzanne, Stringer Sven, Watanabe Kyoko, Jansen Philip R, Coleman Jonathan R I, Krapohl Eva, Taskesen Erdogan, Hammerschlag Anke R, Okbay Aysu, Zabaneh Delilah, Amin Najaf, Breen Gerome, Cesarini David, Chabris Christopher F, Iacono William G, Ikram M Arfan, Johannesson Magnus, Koellinger Philipp, Lee James J, Magnusson Patrik K E, McGue Matt, Miller Mike B, Ollier William E R, Payton Antony, Pendleton Neil, Plomin Robert, Rietveld Cornelius A, Tiemeier Henning, van Duijn Cornelia M, Posthuma Danielle
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.
Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands.
Nat Genet. 2017 Jul;49(7):1107-1112. doi: 10.1038/ng.3869. Epub 2017 May 22.
Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10). Despite the well-known difference in twin-based heritability for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (r = 0.89, LD score regression P = 5.4 × 10). These findings provide new insight into the genetic architecture of intelligence.
智力与重要的经济和健康相关生活结果相关。尽管智力具有较高的遗传力（0.54）且已证实具有多基因性质，但最初的基因研究大多样本量不足。在此，我们报告一项对78308名个体的智力进行的荟萃分析。我们在18个基因组位点中鉴定出336个相关的单核苷酸多态性（METAL P < 5×10），其中15个是新发现的。约一半的单核苷酸多态性位于基因内部，涉及22个基因，其中11个是新发现。基于基因的分析又鉴定出30个基因（MAGMA P < 2.73×10），其中除一个外此前均未被涉及。我们表明，所鉴定的基因主要在脑组织中表达，通路分析表明涉及调控细胞发育的基因（MAGMA竞争P = 3.5×10）。尽管众所周知儿童期（0.45）和成年期（0.80）基于双胞胎的智力遗传力存在差异，但我们显示出显著的遗传相关性（r = 0.89，LD评分回归P = 5.4×10）。这些发现为智力的遗传结构提供了新的见解。
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