胼胝体亚区的分布遗传效应表明与神经精神障碍和相关特征有关。

IF 3.8 4区 医学 Q1 Medicine
Megan L Campbell, Shareefa Dalvie, Alexey Shadrin, Dennis van der Meer, Kevin O'Connell, Oleksander Frei, Ole A Andreassen, Dan J Stein, Jaroslav Rokicki
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引用次数: 0

摘要

背景:胼胝体(CC)是一种具有高遗传性的大脑结构,在精神疾病中具有潜在作用。然而,CC的遗传结构以及与精神疾病的遗传联系在很大程度上仍不清楚。我们研究了CC及其亚区体积的遗传结构,以及与精神疾病的遗传重叠。方法:我们将多变量全基因组关联研究(GWAS)应用于英国生物库40894名个体的遗传和T1加权磁共振成像(MRI)数据,旨在促进基因发现,并评估FreeSurfer 7.1获得的CC五个亚区(后部、中后部、中央、中前部和前部)体积的多效性效应。多变量GWAS结合所有子区域运行,相关变量共同变化。使用MAGMA进行基因集富集分析。采用连锁不平衡评分回归法(LDSC)测定了基于单核苷酸多态性(SNP)的CC总体积及其亚区体积的遗传力及其与相关精神特征的遗传相关性。结果:我们鉴定了70个独立的基因座,这些基因座在CC的五个亚区具有分布效应(p<5×10-8)。此外,我们在前部亚区确定了33个重要位点,23个在前部中部,29个在中部,7个在后部,56个在后部亚区。基因集分析显示156个显著基因对CC亚区的体积有贡献(p<2.6×10-6)。LDSC估计CC的遗传力为(h2SNP=0.38,SE=0.03),亚区范围为0.22(SE=0.02)至0.37(SE=0.03),BD的中前部亚区体积(rg=0.12,SE=0.02;p=2.5×10-4)、重度抑郁障碍(MDD)(rg=0.12中,SE=0.04;p=3.6×10-3),每周饮酒量(rg=0.13,SE=0.04;p=1.8×10-3)和大麻使用量(rg=0.09,SE=0.03;p=8.4×10-3。我们发现,不同的遗传因素参与了前部和后部亚区的发育,这与它们不同的功能专长一致。CC和BD量、每周饮酒量、MDD和大麻消费亚区域量与精神特征之间存在显著的遗传相关性,值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Distributed genetic effects of the corpus callosum subregions suggest links to neuropsychiatric disorders and related traits.

Background: The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remain largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions and the genetic overlap with psychiatric disorders.

Methods: We applied multivariate genome-wide association study (GWAS) to genetic and T1-weighted magnetic resonance imaging (MRI) data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid-posterior, central, mid-anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine Single nucleotide polymorphism (SNP)-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits.

Results: We identified 70 independent loci with distributed effects across the five subregions of the CC (p < 5 × 10-8). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid-anterior, 29 in the central, 7 in the mid-posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (p < 2.6 × 10-6). LDSC estimated the heritability of CC to (h2SNP = 0.38, SE = 0.03) and subregions ranging from 0.22 (SE = 0.02) to 0.37 (SE = 0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, rg = -0.09, SE = 0.03; p = 5.9 × 10-3) and drinks consumed per week (rg = -0.09, SE = 0.02; p = 4.8 × 10-4), and volume of the mid-anterior subregion with BD (rg = -0.12, SE = 0.02; p = 2.5 × 10-4), major depressive disorder (MDD) (rg = -0.12, SE = 0.04; p = 3.6 × 10-3), drinks consumed per week (rg = -0.13, SE = 0.04; p = 1.8 × 10-3) and cannabis use (rg = -0.09, SE = 0.03; p = 8.4 × 10-3).

Conclusions: Our results demonstrate that the CC has a polygenic architecture implicating multiple genes and show that CC subregion volumes are heritable. We found that distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialisation. Significant genetic correlation between volumes of the CC and BD, drinks per week, MDD and cannabis consumption subregion volumes with psychiatric traits is noteworthy and deserving of further investigation.

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来源期刊
Acta Neuropsychiatrica
Acta Neuropsychiatrica 医学-精神病学
CiteScore
8.50
自引率
5.30%
发文量
30
审稿时长
6-12 weeks
期刊介绍: Acta Neuropsychiatrica is an international journal focussing on translational neuropsychiatry. It publishes high-quality original research papers and reviews. The Journal''s scope specifically highlights the pathway from discovery to clinical applications, healthcare and global health that can be viewed broadly as the spectrum of work that marks the pathway from discovery to global health.
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