Obsessive-compulsive disorder (OCD) represents a heterogeneous collection of diseases with diverse levels of phenotypic, genetic, and etiologic variability, making it difficult to identify the underlying genetic and biological mechanisms in humans. Domestic dogs exhibit several OCD-like behaviors. Using continuous circling as a representative phenotype for OCD, we screened two independent dog breeds, the Belgian Malinois and Kunming Dog and subsequently sequenced ten circling dogs and ten unaffected dogs for each breed. Using population differentiation analyses, we identified 11 candidate genes in the extreme tail of the differentiated regions between cases and controls. These genes overlap significantly with genes identified in a genome wide association study (GWAS) of human OCD, indicating strong convergence between humans and dogs. Through gene expressional analysis and functional exploration, we found that two candidate OCD risk genes, PPP2R2B and ADAMTSL3, affected the density and morphology of dendritic spines. Therefore, changes in dendritic spine may underlie some common biological and physiological pathways shared between humans and dogs. Our study revealed an unprecedented level of convergence in OCD shared between humans and dogs, and highlighted the importance of using domestic dogs as a model species for many human diseases including OCD.

强迫症 (OCD) 代表了一系列具有不同表型、遗传和病因变异性的疾病，因此很难确定人类潜在的遗传和生物学机制。家犬表现出几种类似强迫症的行为。使用连续盘旋作为强迫症的代表性表型，我们筛选了两个独立的犬种，比利时玛利诺犬和昆明犬，随后对每个品种的十只盘旋犬和十只未受影响的犬进行了测序。使用种群分化分析，我们在病例和对照之间的分化区域的极端尾部确定了 11 个候选基因。这些基因与人类强迫症的全基因组关联研究 (GWAS) 中确定的基因显着重叠，表明人与狗之间存在强烈的趋同性。PPP2R2B和ADAMTSL3影响树突棘的密度和形态。因此，树突棘的变化可能是人类和狗之间共有的一些共同生物和生理途径的基础。我们的研究揭示了人类和狗之间共有的强迫症前所未有的趋同程度，并强调了使用家犬作为包括强迫症在内的许多人类疾病的模式物种的重要性。