Verebi Camille, Lebrun Nicolas, Petit Justine Vily, Viltart Odile, Duriez Philibert, Saint-Pierre Benjamin, Gorwood Philip, Ramoz Nicolas, Bienvenu Thierry
Service de Médecine Génomique des maladies de système et d'organe, Hôpital Cochin, Assistance Publique, Centre Université de Paris Cité, Paris, France.
Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM UMR1266, Gorwood Team, Université de Paris Cité, Paris, France.
Am J Med Genet B Neuropsychiatr Genet. 2025 Jun;198(4):e33018. doi: 10.1002/ajmg.b.33018. Epub 2024 Dec 11.
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.
神经性厌食症（AN）是一种精神疾病，其遗传度估计约为70%。尽管对AN进行的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遗传基础背后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核细胞进行了转录组分析。我们在模拟AN若干方面的慢性食物限制小鼠模型中验证了我们的平均结果。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，我们鉴定出七个先前发现的在AN个体的诱导多能干细胞衍生神经元中失调的基因以及Vanin-1（Vnn1）基因，该基因似乎在几种代谢途径的调节中起重要作用。我们在慢性食物限制小鼠模型中证实了Vnn1的表达下调，尤其是在肝脏中。这些结果表明，定量食物限制会影响Vnn1的表达，这表明该基因可能在慢性食物限制小鼠模型以及AN患者的厌食表型中起作用。我们相信本报告突出了AN有前景的候选基因和基因途径，并且尽管我们在重复队列中未获得显著结果，但它将Vnn1鉴定为一种潜在的生物标志物，可作为预测和/或理解AN的分子靶点。
