Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence.
Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence.
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DOI：
10.1038/ng.3869
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发表时间：
2017-07
期刊：
影响因子：
30.8
通讯作者：
Posthuma D
中科院分区：
文献类型：
--
作者：
Sniekers S;Stringer S;Watanabe K;Jansen PR;Coleman JRI;Krapohl E;Taskesen E;Hammerschlag AR;Okbay A;Zabaneh D;Amin N;Breen G;Cesarini D;Chabris CF;Iacono WG;Ikram MA;Johannesson M;Koellinger P;Lee JJ;Magnusson PKE;McGue M;Miller MB;Ollier WER;Payton A;Pendleton N;Plomin R;Rietveld CA;Tiemeier H;van Duijn CM;Posthuma D
智力与重要的经济和健康相关的生活结果有关1。尽管智力有很大的遗传性2（0.54）和确认多基因的性质，最初的遗传研究大多是动力不足3，4，5。在这里，我们报告了对78，308人的智力进行的荟萃分析。我们在18个基因组位点中鉴定了336个相关的SNP（金属P< 5× 10− 8），其中15个是新的。大约一半的SNP位于基因内部，涉及22个基因，其中11个是新发现。基于基因的分析确定了另外30个基因（MAGMA P< 2.73× 10− 6），其中除了一个基因之外，其他所有基因都没有被发现。我们发现，所鉴定的基因主要在脑组织中表达，通路分析表明参与调节细胞发育的基因（MAGMA竞争性P= 3.5× 10− 6）。尽管儿童期（0.45）和成年期（0.80）的双胞胎智力遗传力2存在众所周知的差异，但我们发现了大量的遗传相关性（r g= 0.89，LD评分回归P= 5.4× 10− 29）。这些发现为智力的遗传结构提供了新的见解。
Intelligence is associated with important economic and health-related life outcomes 1. Despite intelligence having substantial heritability 2 (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered 3, 4, 5. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P< 5× 10− 8) 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− 6), 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− 6). Despite the well-known difference in twin-based heritability 2 for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (r g= 0.89, LD score regression P= 5.4× 10− 29). These findings provide new insight into the genetic architecture of intelligence.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
11
作者：
Davies G;Marioni RE;Liewald DC;Hill WD;Hagenaars SP;Harris SE;Ritchie SJ;Luciano M;Fawns-Ritchie C;Lyall D;Cullen B;Cox SR;Hayward C;Porteous DJ;Evans J;McIntosh AM;Gallacher J;Craddock N;Pell JP;Smith DJ;Gale CR;Deary IJ
通讯作者：
Deary IJ
影响因子：
3.7
作者：
Comuzzie AG;Cole SA;Laston SL;Voruganti VS;Haack K;Gibbs RA;Butte NF
通讯作者：
Butte NF
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：
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