利用多基因神经成像衍生评分探索大脑结构和多动症的遗传结构。

IF 1.6 3区 医学 Q3 GENETICS & HEREDITY
Tim van der Es, Sourena Soheili-Nezhad, Nina Roth Mota, Barbara Franke, Jan Buitelaar, Emma Sprooten
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引用次数: 0

摘要

全基因组关联研究(GWAS)为了解神经精神疾病的遗传基础提供了宝贵的见解,并凸显了其复杂性。仔细考虑多基因性和复杂的遗传结构有助于了解潜在的大脑机制。我们引入了一种创新的多基因评分方法,利用成像衍生表型(IDP)来预测临床表型。我们利用英国生物库中的 IDP GWAS 数据创建了多基因成像衍生评分(PIDS)。作为概念验证,我们评估了多动症患者与未受影响的对照组之间大脑结构的遗传变异,共涉及三次神经影像图像波(n = 954)。在 94 个 PIDS 中,有 72 个与独立样本中相应的 IDPs 有显著关联。值得注意的是,包括小脑白质、小脑皮质和大脑白质在内的几种全局性测量指标显示出其各自的 IDPs 有很大的方差解释率,从 3% 到 5.7% 不等。相反,每个 IDP 与临床多动症表型之间的关联相对较弱。这些发现凸显了全球基因组学分析在结构性神经影像特征方面日益强大的作用,它可以构建多基因评分,准确反映潜在的多基因结构。然而,要在 PIDS 与行为或临床特征(如多动症)之间建立稳固的联系,还需要更大的样本。我们的多基因风险评分新方法为精神遗传学领域的研究人员提供了一种宝贵的工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Exploring the genetic architecture of brain structure and ADHD using polygenic neuroimaging-derived scores

Exploring the genetic architecture of brain structure and ADHD using polygenic neuroimaging-derived scores

Genome-wide association studies (GWAS) have provided valuable insights into the genetic basis of neuropsychiatric disorders and highlighted their complexity. Careful consideration of the polygenicity and complex genetic architecture could aid in the understanding of the underlying brain mechanisms. We introduce an innovative approach to polygenic scoring, utilizing imaging-derived phenotypes (IDPs) to predict a clinical phenotype. We leveraged IDP GWAS data from the UK Biobank, to create polygenic imaging-derived scores (PIDSs). As a proof-of-concept, we assessed genetic variations in brain structure between individuals with ADHD and unaffected controls across three NeuroIMAGE waves (n = 954). Out of the 94 PIDS, 72 exhibited significant associations with their corresponding IDPs in an independent sample. Notably, several global measures, including cerebellum white matter, cerebellum cortex, and cerebral white matter, displayed substantial variance explained for their respective IDPs, ranging from 3% to 5.7%. Conversely, the associations between each IDP and the clinical ADHD phenotype were relatively weak. These findings highlight the growing power of GWAS in structural neuroimaging traits, enabling the construction of polygenic scores that accurately reflect the underlying polygenic architecture. However, to establish robust connections between PIDS and behavioral or clinical traits such as ADHD, larger samples are needed. Our novel approach to polygenic risk scoring offers a valuable tool for researchers in the field of psychiatric genetics.

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来源期刊
CiteScore
5.90
自引率
7.10%
发文量
40
审稿时长
4-8 weeks
期刊介绍: Neuropsychiatric Genetics, Part B of the American Journal of Medical Genetics (AJMG) , provides a forum for experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders. It is a resource for novel genetics studies of the heritable nature of psychiatric and other nervous system disorders, characterized at the molecular, cellular or behavior levels. Neuropsychiatric Genetics publishes eight times per year.
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