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肥胖的神经行为相关性在很大程度上是可遗传的。

Neurobehavioral correlates of obesity are largely heritable.

机构信息

Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.

Institute of Psychology, University of Tartu, Näituse 2, 50409 Tartu, Estonia.

出版信息

Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):9312-9317. doi: 10.1073/pnas.1718206115. Epub 2018 Aug 28.

Abstract

Recent molecular genetic studies have shown that the majority of genes associated with obesity are expressed in the central nervous system. Obesity has also been associated with neurobehavioral factors such as brain morphology, cognitive performance, and personality. Here, we tested whether these neurobehavioral factors were associated with the heritable variance in obesity measured by body mass index (BMI) in the Human Connectome Project ( = 895 siblings). Phenotypically, cortical thickness findings supported the "right brain hypothesis" for obesity. Namely, increased BMI is associated with decreased cortical thickness in right frontal lobe and increased thickness in the left frontal lobe, notably in lateral prefrontal cortex. In addition, lower thickness and volume in entorhinal-parahippocampal structures and increased thickness in parietal-occipital structures in participants with higher BMI supported the role of visuospatial function in obesity. Brain morphometry results were supported by cognitive tests, which outlined a negative association between BMI and visuospatial function, verbal episodic memory, impulsivity, and cognitive flexibility. Personality-BMI correlations were inconsistent. We then aggregated the effects for each neurobehavioral factor for a behavioral genetics analysis and estimated each factor's genetic overlap with BMI. Cognitive test scores and brain morphometry had 0.25-0.45 genetic correlations with BMI, and the phenotypic correlations with BMI were 77-89% explained by genetic factors. Neurobehavioral factors also had some genetic overlap with each other. In summary, obesity as measured by BMI has considerable genetic overlap with brain and cognitive measures. This supports the theory that obesity is inherited via brain function and may inform intervention strategies.

摘要

最近的分子遗传学研究表明,与肥胖相关的大多数基因都在中枢神经系统中表达。肥胖也与神经行为因素有关,如大脑形态、认知表现和个性。在这里,我们测试了这些神经行为因素是否与人类连接组计划(n = 895 对兄弟姐妹)中通过体重指数(BMI)测量的肥胖的可遗传性变异有关。表型上,皮质厚度的发现支持肥胖的“右脑假说”。也就是说,BMI 越高,与右侧额叶皮质厚度降低和左侧额叶皮质厚度增加有关,特别是在外侧前额叶皮层。此外,参与者 BMI 越高,其内侧额-海马结构的厚度越低,顶叶-枕叶结构的厚度越高,这支持了肥胖与视空间功能的关系。大脑形态学结果得到认知测试的支持,认知测试表明 BMI 与视空间功能、情景记忆、冲动性和认知灵活性呈负相关。人格与 BMI 的相关性不一致。然后,我们为每个神经行为因素汇总了效应,进行行为遗传学分析,并估计了每个因素与 BMI 的遗传重叠。认知测试分数和大脑形态学与 BMI 的遗传相关性为 0.25-0.45,与 BMI 的表型相关性有 77-89%可由遗传因素解释。神经行为因素之间也存在一定的遗传重叠。总的来说,BMI 所衡量的肥胖与大脑和认知测量有相当大的遗传重叠。这支持了肥胖是通过大脑功能遗传的理论,并可能为干预策略提供信息。

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