神经性厌食症潜在的新表达生物标志物。

IF 1.6 3区 医学 Q3 GENETICS & HEREDITY
Camille Verebi, Nicolas Lebrun, Justine Vily Petit, Odile Viltart, Philibert Duriez, Benjamin Saint-Pierre, Philip Gorwood, Nicolas Ramoz, Thierry Bienvenu
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引用次数: 0

摘要

神经性厌食症(AN)是一种精神疾病,估计遗传率约为70%。尽管对AN全基因组关联研究的最大荟萃分析确定了该疾病的独立风险赋予位点,但AN遗传基础的分子机制仍有待阐明。为了研究AN,我们对15名AN患者和15名健康对照者的外周血单个核细胞进行了转录组分析。我们在慢性食物限制的小鼠模型中验证了我们的平均结果,该模型模拟了AN的几个方面。在这项探索性研究中,我们在AN中鉴定出673个显著差异表达的基因。在这些基因中,我们发现了7个先前发现在AN个体的ipsc衍生神经元中失调的基因和Vanin-1 (Vnn1)基因,该基因似乎在几种代谢途径的调节中发挥重要作用。我们在慢性食物限制小鼠模型中证实了Vnn1的低表达,特别是在肝脏中。这些结果表明,定量食物限制会影响Vnn1的表达,表明该基因可能有助于慢性食物限制小鼠模型和AN患者的厌食表型。我们认为这篇报道强调了AN有希望的候选基因和基因通路,尽管我们没有在复制队列中获得显著的结果,但它确定了Vnn1作为一个潜在的生物标志物,可以用作预测和/或理解AN的分子靶标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Potential New Expression Biomarkers for Anorexia Nervosa.

Anorexia nervosa (AN) is a psychiatric disorder with an estimated heritability of around 70%. Although the largest meta-analysis of genome-wide association studies on AN identified independent risk-conferring loci for the disorder, the molecular mechanisms underlying the genetic basis of AN remain to be elucidated. To investigate AN, we performed transcriptome profiling in peripheral blood mononuclear cells from 15 AN patients and 15 healthy controls. We validated our mean results in a mouse model of chronic food restriction, which mimics several aspects of AN. In this exploratory study, we identified 673 significantly differentially expressed genes in AN. Among these genes, we identified seven genes previously found to be dysregulated in IPSC-derived neurons from AN individuals and the Vanin-1 (Vnn1) gene, which appears to play an important role in the regulation of several metabolic pathways. We confirmed underexpression of Vnn1, particularly in the liver, in a mouse model of chronic food restriction. These results indicate that quantitative food restriction affects Vnn1 expression, suggesting that this gene may contribute to the anorexic phenotype in the chronic food restriction mouse model as well as in patients with AN. We believe that this report highlights promising candidate genes and gene pathways for AN, and although we did not obtain a significant result in the replication cohort, it identifies Vnn1 as a potential biomarker that may be used as a molecular target to predict and/or to understand AN.

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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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