Nat Genet：新基因HMGA2关联大脑尺寸及智力

在全世界最大规模的脑研究中，由来自全世界100个研究机构的200多个研究人员组成的研究小组，共同绘制出一些人类基因，这些基因有的促进大脑抵抗各种精神疾病与阿尔茨海默病，有的破坏大脑对那些疾病的抵抗。相关研究结果发表在4月15日在线版Nature Genetics上，揭示了用来解释大脑大小与智力个体差异的新基因。

研究人员不仅探讨增加单一疾病遗传风险的基因，也对导致组织萎缩和大脑尺寸减小的因素进行了研究，也就是遗传性疾病生物学标志，这里的遗传性疾病主要是精神分裂症、双相性精神障碍、抑郁症、阿尔茨海默症和痴呆。同时，还特别地寻找出使健康人脑组织超常耗竭的基因变异。此项目规模庞大，足以使研究小组发掘某些人的新遗传变异，这些人不但有更大体积的大脑，而且学习记忆关键域存在差异。结果发现，有一种统一联系，该联系存在遗传密码细微变化与记忆中心缩减之间，即：HMGA2基因的一个变异既影响大脑尺寸，也影响智力。若某人HMGA2基因上T碱基被C碱基替代，他就会有一个尺寸较大的大脑，在标准IQ测试中得分也高得多。

此研究提供了相当明确的证据，来证明大脑功能、智力与遗传的关联。因为，像阿尔茨海默症、孤独症及精神分裂症这样的疾病能瓦解大脑“电路系统”，所以，下一步将要搜寻出那些影响大脑连线的基因。

doi:10.1038/ng.2250
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Identification of common variants associated with human hippocampal and intracranial volumes

Jason L Stein, Sarah E Medland, Alejandro Arias Vasquez, Derrek P Hibar, Rudy E Senstad,Anderson M Winkler, Roberto Toro, Katja Appel, Richard Bartecek, ?rjan Bergmann, Manon Bernard, Andrew A Brown, Dara M Cannon, M Mallar Chakravarty, Andrea Christoforou, Martin Domin, Oliver Grimm, Marisa Hollinshead, Avram J Holmes, Georg Homuth, Jouke-Jan Hottenga,Camilla Langan, Lorna M Lopez, Narelle K Hansell, Kristy S Hwang et al.

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease1, 2 and is reduced in schizophrenia3, major depression4 and mesial temporal lobe epilepsy5. Whereas many brain imaging phenotypes are highly heritable6, 7, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10^-16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10^-12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10^-7).