The human brain remains active in the absence of explicit tasks and forms networks of correlated activity. Resting-state functional magnetic resonance imaging (rsfMRI) measures brain activity at rest, which has been linked with both cognitive and clinical outcomes. The genetic variants influencing human brain function are largely unknown. Here we utilized rsfMRI from 44,190 individuals of multiple ancestries (37,339 in the UK Biobank) to discover and validate the common genetic variants influencing intrinsic brain activity. We identified hundreds of novel genetic loci associated with intrinsic functional signatures (P < 2.8 × 10⁻¹¹), including associations to the central executive, default mode, and salience networks involved in the triple network model of psychopathology. A number of intrinsic brain activity associated loci colocalized with brain disorder GWAS (e.g., Alzheimer’s disease, Parkinson’s disease, schizophrenia) and cognition, such as 19q13.32, 17q21.31, and 2p16.1. Particularly, we detected a colocalization between one (rs429358) of the two variants in the APOE ε4 locus and function of the default mode, central executive, attention, and visual networks. Genetic correlation analysis demonstrated shared genetic influences between brain function and brain structure in the same regions. We also detected significant genetic correlations with 26 other complex traits, such as ADHD, major depressive disorder, schizophrenia, intelligence, education, sleep, subjective well-being, and neuroticism. Common variants associated with intrinsic brain activity were enriched within regulatory element in brain tissues.

中文翻译：

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常见变体有助于内在的人类大脑功能网络

人脑在没有明确任务的情况下仍保持活跃，并形成相关活动的网络。静止状态功能磁共振成像（rsfMRI）可以测量静止状态下的大脑活动，这与认知和临床结果均相关。影响人类大脑功能的遗传变异在很大程度上尚不清楚。在这里，我们利用来自44,190个不同祖先个体的rsfMRI（在UK Biobank中为37,339）来发现和验证影响内在大脑活动的常见遗传变异。我们鉴定了数百个与内在功能特征相关的新型遗传基因座（P <2.8×10 ^-11），包括与心理病理学三重网络模型相关的中央执行官，默认模式和显着网络的关联。许多与大脑疾病GWAS（例如，阿尔茨海默氏病，帕金森氏病，精神分裂症）和认知（例如19q13.32、17q21.31和2p16.1）共定位的内在大脑活动相关基因座。特别是，我们在APOE中检测到两个变体之一（rs429358）之间的共定位ε4的位置和功能（默认模式，中央执行器，注意力和视觉网络）。遗传相关分析表明，同一区域的大脑功能和大脑结构之间存在共同的遗传影响。我们还检测到与26种其他复杂性状的显着遗传相关性，例如多动症，严重抑郁症，精神分裂症，智力，教育，睡眠，主观幸福感和神经质。与内在的大脑活动相关的常见变异丰富了大脑组织中的调节元件。