Department of Veterinary Biosciences, University of Helsinki, 00014, Helsinki, Finland.
Research Programs Unit, Molecular Neurology, University of Helsinki, 00014, Helsinki, Finland.
Transl Psychiatry. 2019 Jan 17;9(1):18. doi: 10.1038/s41398-018-0361-x.
Anxiety disorders are among the leading health issues in human medicine. The complex phenotypic and allelic nature of these traits as well as the challenge of establishing reliable measures of the heritable component of behaviour from the associated environmental factors hampers progress in their molecular aetiology. Dogs exhibit large natural variation in fearful and anxious behaviour and could facilitate progress in the molecular aetiology due to their unique genetic architecture. We have performed a genome-wide association study with a canine high-density SNP array in a cohort of 330 German Shepherds for two phenotypes, fear of loud noises (noise sensitivity) and fear of strangers or in novel situations. Genome-widely significant loci were discovered for the traits on chromosomes 20 and 7, respectively. The regions overlap human neuropsychiatric loci, including 18p11.2, with physiologically relevant candidate genes that contribute to glutamatergic and dopaminergic neurotransmission in the brain. In addition, the noise-sensitivity locus includes hearing-related candidate genes. These results indicate a genetic contribution for canine fear and suggest a shared molecular aetiology of anxiety across species. Further characterisation of the identified loci will pave the way to molecular understanding of the conditions as a prerequisite for improved therapy.
焦虑症是人类医学中的主要健康问题之一。这些特征的复杂表型和等位基因性质，以及从相关环境因素中确定行为遗传成分的可靠测量方法的挑战，阻碍了它们的分子发病机制的研究进展。狗在恐惧和焦虑行为方面表现出很大的自然变异，由于其独特的遗传结构，它们可能有助于分子发病机制的研究进展。我们对一个由 330 只德国牧羊犬组成的队列进行了一项全基因组关联研究，使用了犬类高密度 SNP 阵列，研究了两种表型，即对巨响的恐惧（噪音敏感）和对陌生人或新环境的恐惧。分别在第 20 号和第 7 号染色体上发现了与这些特征相关的全基因组显著位点。这些区域与人类神经精神疾病相关的位点重叠，包括 18p11.2，其中有与大脑中谷氨酸能和多巴胺能神经传递相关的生理相关候选基因。此外，噪音敏感位点包括与听力相关的候选基因。这些结果表明犬类恐惧存在遗传因素，并表明焦虑在物种间具有共同的分子发病机制。对已确定的基因座的进一步特征描述将为分子理解这些疾病铺平道路，这是改善治疗的前提。
