图片来源：Pixabay 科学家们很早就知道，人类会从父母那里遗传智力和一些人格障碍，与此同时环境因素（例如教育、压力等）也会在智力、心理健康塑造上产生重要影响。但是，遗传学家很难确定与智力相关的基因。 2017年，阿姆斯特丹自由大学的遗传学家Danielle Posthuma带领团队研发了新的统计方法，可以在庞大的数据库中检测到某些基因与特定特征之间的紧密联系。他们在8万人的数据中筛选到与智力相关的52个基因。（详细） 现在，Danielle Posthuma团队在“智力基因”列表中新添加了近1000个成员。他们检索了14个数据库，在250000个人的健康记录中找到了939个与智力相关的新基因。
https:///10.1038/s41588-018-0151-7 很多与高智商有关的基因变异会让人更长寿，且不会发生阿尔兹海默症、注意力缺陷症或者精神分裂症。这意味着，这些突变能够预防这些疾病。遗憾的是，它们会增加自闭症的发生风险。 在另一篇同时发表在《Nature Genetics》期刊上的文章中，Danielle Posthuma团队分析了449,400个人的健康和基因数据，从中共找到500个与神经质（neurotic traits）有关的基因，例如焦虑、抑郁。
https:///10.1038/s41588-018-0152-6 在这两项研究中，科学家们使用了一种新的统计方法——MAGMA，能够快速搜索基因数据并识别有基因表达的特定细胞和组织。研究发现，中型棘突神经元（medium spiny neurons，基底神经元的一部分）表达有许多智力基因。此外，他们还找到了不少可开发成药物的潜在靶标。 这两项研究提供了首份证据：许多基因和通路以复杂的方式共同努力，构建智慧的大脑并保持平衡。Posthuma认为，智力基因的挖掘有望为预防阿尔兹海默症等疾病提供新的线索。 责编：风铃 参考资料： Hundreds of new genes may underlie intelligence—but also autism and depression
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 Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligenceIntelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3,4,5,6,7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer’s disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders. 展开 Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathwaysNeuroticism is an important risk factor for psychiatric traits, including depression1, anxiety2,3, and schizophrenia4,5,6. At the time of analysis, previous genome-wide association studies7,8,9,10,11,12 (GWAS) reported 16 genomic loci associated to neuroticism10,11,12. Here we conducted a large GWAS meta-analysis (n = 449,484) of neuroticism and identified 136 independent genome-wide significant loci (124 new at the time of analysis), which implicate 599 genes. Functional follow-up analyses showed enrichment in several brain regions and involvement of specific cell types, including dopaminergic neuroblasts (P = 3.49 × 10−8), medium spiny neurons (P = 4.23 × 10−8), and serotonergic neurons (P = 1.37 × 10−7). Gene set analyses implicated three specific pathways: neurogenesis (P = 4.43 × 10−9), behavioral response to cocaine processes (P = 1.84 × 10−7), and axon part (P = 5.26 × 10−8). We show that neuroticism’s genetic signal partly originates in two genetically distinguishable subclusters13 (‘depressed affect’ and ‘worry’), suggesting distinct causal mechanisms for subtypes of individuals. Mendelian randomization analysis showed unidirectional and bidirectional effects between neuroticism and multiple psychiatric traits. These results enhance neurobiological understanding of neuroticism and provide specific leads for functional follow-up experiments. |
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