Fang Antoinette, Kumar Lakshin, Creevy Kate E, Promislow Daniel E L, Ma Jing
Department of Mathematics, University of Chicago, Chicago, Illinois, United States of America.
Department of Medicine, University of California, San Francisco, California, United States of America.
PLoS Comput Biol. 2025 Aug 14;21(8):e1012728. doi: 10.1371/journal.pcbi.1012728. eCollection 2025 Aug.
Comorbidity and its association with age are of great interest in geroscience. However, there are few model organisms that are well-suited to study comorbidities that will have high relevance to humans. In this light, we turn our attention to the companion dog. The companion dog shares many morbidities with humans. Thus, a better understanding of canine comorbidity relationships could benefit both humans and dogs. We present an analysis of canine comorbidity networks from the Dog Aging Project, a large epidemiological cohort study of companion dogs in the United States. We included owner-reported health conditions that occurred in at least 60 dogs (n = 160) and included only dogs that had at least one of those health conditions (n = 26,614). We constructed an undirected comorbidity network using a Poisson binomial test, adjusting for age, sex, sterilization status, breed background (i.e., purebred vs. mixed-breed), and weight. The comorbidity network reveals well-documented comorbidities, such as diabetes with cataracts and blindness, and hypertension with chronic kidney disease (CKD). In addition, this network also supports less well-studied comorbidity relationships, such as proteinuria with anemia. A directed comorbidity network accounting for time of reported condition onset suggests that diabetes precedes cataracts, elbow/hip dysplasia before osteoarthritis, and keratoconjunctivitis sicca before corneal ulcer, which are consistent with the canine literature. Analysis of age-stratified networks reveals that global centrality measures increase with age and are the highest in the Senior group compared to the Young Adult and Mature Adult groups. Only the Senior group identified the association between hypertension and CKD. Our results suggest that comorbidity network analysis is a promising method to enhance clinical knowledge and canine healthcare management.
共病及其与年龄的关联在老年科学中备受关注。然而，很少有适合研究与人类高度相关共病的模式生物。鉴于此，我们将注意力转向宠物犬。宠物犬与人类有许多共同的疾病。因此，更好地理解犬类共病关系对人类和犬类都有益。我们对来自美国一项针对宠物犬的大型流行病学队列研究——犬类衰老项目中的犬类共病网络进行了分析。我们纳入了至少60只犬（n = 160）出现的、由主人报告的健康状况，且仅纳入至少有其中一种健康状况的犬（n = 26,614）。我们使用泊松二项式检验构建了一个无向共病网络，并对年龄、性别、绝育状态、品种背景（即纯种与混种）和体重进行了调整。该共病网络揭示了一些有充分文献记载的共病，如糖尿病与白内障和失明，以及高血压与慢性肾病（CKD）。此外，这个网络还支持了一些研究较少的共病关系，如蛋白尿与贫血。一个考虑报告疾病发病时间的有向共病网络表明，糖尿病先于白内障出现，肘部/髋部发育不良先于骨关节炎，干眼症先于角膜溃疡，这与犬类文献一致。对按年龄分层的网络分析表明，全局中心性度量随年龄增加，与青年组和成年组相比，老年组的全局中心性度量最高。只有老年组识别出高血压与CKD之间的关联。我们的结果表明，共病网络分析是一种增强临床知识和犬类医疗管理的有前景的方法。
