Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Spain.
J Psychiatr Res. 2013 Jun;47(6):747-54. doi: 10.1016/j.jpsychires.2012.12.015. Epub 2013 Jan 19.
Several lines of evidence, including psychopathological, neurobiological, pharmacological and epidemiological data, supported the association between Anorexia Nervosa (AN) and Obsessive-Compulsive Disorder (OCD). The aim of the present study is to test the hypothesis of partial common genetic background of both disease, AN and OCD. A total of 116 patients with AN, 74 patients with OCD and 91 controls participated in this study. 213 single-nucleotide polymorphisms (SNPs) in 28 candidate genes were analyzed. Five SNPs achieved 0.004 (the nominal p-value expected by chance), 3 with empirical significant p-values (rs10070190 (CDH9) p = 1 × 10(-3), rs4825476 (GRIA3) p = 4 × 10(-4), and rs1074815 (TPH2) p = 8 × 10(-4)) and 2 additional polymorphisms showing nominal significance (rs2834070 (OLIG2) p = 2 × 10(-3) and rs11783752 (SCL18A1) p = 3 × 10(-3)), were found to be related to both AN and OCD. In addition, rs3825885 (NTRK3, p = 9 × 10(-4)) was identified as an AN risk variant, and rs11179027 (TPH2, p = 2 × 10(-3)) as an OCD marker. The ROC analysis confirmed these results and showed interaction among the significant SNPs. The preliminary results we report here reveal a partial common genetic background in AN and OCD, in agreement with previous clinical findings of common symptomathology between these two diseases and open the field of possible treatments for AN. The interaction observed between the associated polymorphisms, could indicate that there is a biological interaction between the serotonin (TPH2 and SLC18A1) and glutamate (GRIA3) pathways and the factors related to neurogenesis (CDH9, OLIG2 and NTRK3) for the explanation of etiopathophysiology in both diseases. However, the results must be replicated in studies with larger cohorts in order to confirm these associations.
有几条证据，包括精神病理学、神经生物学、药理学和流行病学数据，都支持厌食症 (AN) 和强迫症 (OCD) 之间的关联。本研究的目的是检验这两种疾病（AN 和 OCD）具有部分共同遗传背景的假设。共有 116 名 AN 患者、74 名 OCD 患者和 91 名对照参加了这项研究。分析了 28 个候选基因中的 213 个单核苷酸多态性 (SNP)。有 5 个 SNP 达到了 0.004（随机期望的名义 p 值），其中 3 个具有经验显著的 p 值（rs10070190（CDH9）p=1×10(-3)，rs4825476（GRIA3）p=4×10(-4)，和 rs1074815（TPH2）p=8×10(-4)），另外 2 个多态性显示名义显著（rs2834070（OLIG2）p=2×10(-3)和 rs11783752（SCL18A1）p=3×10(-3)），与 AN 和 OCD 均有关。此外，rs3825885（NTRK3，p=9×10(-4)) 被确定为 AN 风险变异，rs11179027（TPH2，p=2×10(-3)) 为 OCD 标志物。ROC 分析证实了这些结果，并显示了显著 SNP 之间的相互作用。我们这里报告的初步结果显示，AN 和 OCD 具有部分共同的遗传背景，与这两种疾病共同的症状学临床发现一致，并为 AN 的可能治疗开辟了领域。观察到的相关多态性之间的相互作用表明，5-羟色胺（TPH2 和 SLC18A1）和谷氨酸（GRIA3）途径与神经发生（CDH9、OLIG2 和 NTRK3）相关因素之间存在生物学相互作用，以解释这两种疾病的发病机制。然而，为了确认这些关联，需要在更大的队列研究中进行验证。
