{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T23:53:14Z","timestamp":1778629994438,"version":"3.51.4"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["AG057377"],"award-info":[{"award-number":["AG057377"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["AG057377"],"award-info":[{"award-number":["AG057377"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["AG057377"],"award-info":[{"award-number":["AG057377"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001642","name":"Glenn Foundation for Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001642","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tiny Foundation Fund at Myriad Canada"},{"name":"WoodNext Foundation"},{"name":"Dog Aging Institute"},{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"publisher","award":["58-8050-9-004"],"award-info":[{"award-number":["58-8050-9-004"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>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\u2009=\u2009160) and included only dogs that had at least one of those health conditions (n\u2009=\u200926,614). 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.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012728","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T17:25:18Z","timestamp":1755192318000},"page":"e1012728","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Constructing the first comorbidity networks in companion dogs in the Dog Aging Project"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0659-2640","authenticated-orcid":true,"given":"Antoinette","family":"Fang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lakshin","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate E.","family":"Creevy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E.L.","family":"Promislow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6294-227X","authenticated-orcid":true,"given":"Jing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Dog Aging Project Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"issue":"4","key":"pcbi.1012728.ref001","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1370\/afm.983","article-title":"Defining comorbidity: implications for understanding health and health services","volume":"7","author":"JM Valderas","year":"2009","journal-title":"Ann Fam Med"},{"issue":"7","key":"pcbi.1012728.ref002","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/0021-9681(70)90054-8","article-title":"The pre-therapeutic classification of co-morbidity in chronic disease","volume":"23","author":"AR Feinstein","year":"1970","journal-title":"J Chronic Dis"},{"issue":"11","key":"pcbi.1012728.ref003","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1136\/thoraxjnl-2017-210822","article-title":"Predicting risk of unplanned hospital readmission in survivors of critical illness: a population-level cohort study","volume":"74","author":"NI Lone","year":"2019","journal-title":"Thorax"},{"issue":"6","key":"pcbi.1012728.ref004","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1109\/TCBB.2018.2827029","article-title":"Predicting hospital readmission via cost-sensitive deep learning","volume":"15","author":"H Wang","year":"2018","journal-title":"IEEE\/ACM Trans Comput Biol Bioinform"},{"key":"pcbi.1012728.ref005","doi-asserted-by":"crossref","first-page":"103396","DOI":"10.1016\/j.ijnurstu.2019.103396","article-title":"Continuity of care interventions for preventing hospital readmission of older people with chronic diseases: a meta-analysis","volume":"101","author":"G Facchinetti","year":"2020","journal-title":"Int J Nurs Stud"},{"key":"pcbi.1012728.ref006","first-page":"145","article-title":"Intensive care decision making: using prognostic models for resource allocation","volume":"251","author":"A Atashi","year":"2018","journal-title":"Stud Health Technol Inform"},{"issue":"3","key":"pcbi.1012728.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21926\/obm.geriatr.2003127","article-title":"Ageing, comorbidity and frailty-synergistic risk factors for Covid-19 adverse outcomes","volume":"4","author":"D Emmerton","year":"2020","journal-title":"OBM Geriatr"},{"issue":"4","key":"pcbi.1012728.ref008","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1183\/09031936.00059814","article-title":"Ageing and the epidemiology of multimorbidity","volume":"44","author":"MJ Divo","year":"2014","journal-title":"Eur Respir J"},{"issue":"3","key":"pcbi.1012728.ref009","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/gerona\/62.3.275","article-title":"Report of the National Institute on Aging Task Force on Comorbidity","volume":"62","author":"R Yancik","year":"2007","journal-title":"J Gerontol Ser A"},{"issue":"3","key":"pcbi.1012728.ref010","doi-asserted-by":"crossref","DOI":"10.1093\/gerona\/glu113","article-title":"Comorbidity and functional trajectories from midlife to old age: The health and retirement study","volume":"70","author":"S Stenholm","year":"2015","journal-title":"J Gerontol Ser A"},{"issue":"2","key":"pcbi.1012728.ref011","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.critrevonc.2008.01.013","article-title":"The changing prevalence of comorbidity across the age spectrum","volume":"67","author":"JF Piccirillo","year":"2008","journal-title":"Crit Rev Oncol Hematol"},{"key":"pcbi.1012728.ref012","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/978-3-642-15020-3_10","article-title":"A comorbidity network approach to predict disease risk.","volume-title":"Information Technology in Bio- and Medical Informatics, ITBAM 2010","author":"F Folino","year":"2010"},{"issue":"21","key":"pcbi.1012728.ref013","doi-asserted-by":"crossref","first-page":"8685","DOI":"10.1073\/pnas.0701361104","article-title":"The human disease network","volume":"104","author":"KI Goh","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pcbi.1012728.ref014","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1000353","article-title":"A dynamic network approach for the study of human phenotypes","volume":"5","author":"CA Hidalgo","year":"2009","journal-title":"PLOS Comput Biol"},{"issue":"8","key":"pcbi.1012728.ref015","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1002141","article-title":"Using electronic patient records to discover disease correlations and stratify patient cohorts","volume":"7","author":"FS Roque","year":"2011","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"pcbi.1012728.ref016","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s41109-018-0101-4","article-title":"Statistical methods for constructing disease comorbidity networks from longitudinal inpatient data","volume":"3","author":"B Fotouhi","year":"2018","journal-title":"Appl Netw Sci"},{"issue":"6","key":"pcbi.1012728.ref017","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1093\/bioinformatics\/btu731","article-title":"CytoCom: a Cytoscape app to visualize, query and analyse disease comorbidity networks","volume":"31","author":"MA Moni","year":"2015","journal-title":"Bioinformatics"},{"issue":"10","key":"pcbi.1012728.ref018","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/s43588-021-00141-9","article-title":"A Poisson binomial-based statistical testing framework for comorbidity discovery across electronic health record datasets","volume":"1","author":"G Lemmon","year":"2021","journal-title":"Nat Comput Sci"},{"issue":"1","key":"pcbi.1012728.ref019","doi-asserted-by":"crossref","first-page":"4952","DOI":"10.1038\/s41467-020-18682-4","article-title":"Disease trajectory browser for exploring temporal, population-wide disease progression patterns in 7.2 million Danish patients","volume":"11","author":"T Siggaard","year":"2020","journal-title":"Nat Commun"},{"key":"pcbi.1012728.ref020","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s12920-019-0629-x","article-title":"Analysis of disease comorbidity patterns in a large-scale China population","volume":"12","author":"M Guo","year":"2019","journal-title":"BMC Med Genomics"},{"key":"pcbi.1012728.ref021","doi-asserted-by":"crossref","first-page":"846202","DOI":"10.3389\/fdata.2023.846202","article-title":"Comorbidity network analysis using graphical models for electronic health records","volume":"6","author":"B Zhao","year":"2023","journal-title":"Front Big Data"},{"issue":"7895","key":"pcbi.1012728.ref022","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41586-021-04282-9","article-title":"An open science study of ageing in companion dogs","volume":"602","author":"KE Creevy","year":"2022","journal-title":"Nature"},{"issue":"1","key":"pcbi.1012728.ref023","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1038\/s41598-020-59837-z","article-title":"Prevalence, comorbidity, and breed differences in canine anxiety in 13,700 Finnish pet dogs","volume":"10","author":"M Salonen","year":"2020","journal-title":"Sci Rep"},{"issue":"10","key":"pcbi.1012728.ref024","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.2460\/javma.229.10.1591","article-title":"Signalment factors, comorbidity, and trends in behavior diagnoses in dogs: 1,644 cases (1991-2001)","volume":"229","author":"M Bamberger","year":"2006","journal-title":"J Am Vet Med Assoc"},{"key":"pcbi.1012728.ref025","doi-asserted-by":"crossref","DOI":"10.1016\/j.jveb.2019.04.007","article-title":"Demographics and comorbidity of behavior problems in dogs","volume":"32","author":"I Dinwoodie","year":"2019","journal-title":"J Vet Behav"},{"issue":"11","key":"pcbi.1012728.ref026","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/jsap.12904","article-title":"Canine hyperadrenocorticism associations with signalment, selected comorbidities and mortality within North American veterinary teaching hospitals","volume":"59","author":"JM Hoffman","year":"2018","journal-title":"J Small Anim Pract"},{"issue":"12","key":"pcbi.1012728.ref027","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1136\/vr.103360","article-title":"Epilepsy beyond seizures: a review of the impact of epilepsy and its comorbidities on health-related quality of life in dogs","volume":"177","author":"RMA Packer","year":"2015","journal-title":"Vet Rec"},{"key":"pcbi.1012728.ref028","article-title":"Prevalence of proteinuria in a canine oncology population","author":"RA Prudic","year":"2018","journal-title":"J Small Anim Pract"},{"key":"pcbi.1012728.ref029","article-title":"Successful treatment and management of canine ehrlichiosis-leishmaniosis-heartworm comorbidity","author":"A Leal-Lima","year":"2021","journal-title":"Acta Sci Vet Impr"},{"issue":"2","key":"pcbi.1012728.ref030","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/vsu.12444","article-title":"Idiopathic canine laryngeal paralysis as one sign of a diffuse polyneuropathy: an observational study of 90 cases (2007-2013)","volume":"45","author":"LC Bookbinder","year":"2016","journal-title":"Vet Surg"},{"key":"pcbi.1012728.ref031","volume-title":"The Merck veterinary manual","author":"SE Aiello","year":"2016","edition":"11"},{"key":"pcbi.1012728.ref032","doi-asserted-by":"crossref","DOI":"10.1002\/9781119414612","volume-title":"Common clinical presentations in dogs and cats","author":"RE Englar","year":"2019"},{"issue":"8","key":"pcbi.1012728.ref033","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1093\/trstmh\/trac002","article-title":"Co-infection of intestinal helminths in humans and animals in the Philippines","volume":"116","author":"OT Kajero","year":"2022","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"pcbi.1012728.ref034","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1186\/s13071-015-1167-9","article-title":"The importance of multiparasitism: examining the consequences of co-infections for human and animal health","volume":"8","author":"E Vaumourin","year":"2015","journal-title":"Parasit Vectors"},{"issue":"6","key":"pcbi.1012728.ref035","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0007455","article-title":"The extent, nature, and pathogenic consequences of helminth polyparasitism in humans: A meta-analysis","volume":"13","author":"RE Donohue","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"pcbi.1012728.ref036","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0378-8733(78)90021-7","article-title":"Centrality in social networks conceptual clarification","volume":"1","author":"LC Freeman","year":"1978","journal-title":"Soc Netw"},{"key":"pcbi.1012728.ref037","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780198805090.001.0001","volume-title":"Networks","author":"MEJ Newman","year":"2018","edition":"2"},{"issue":"2","key":"pcbi.1012728.ref038","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0280795","article-title":"Age at cancer diagnosis by breed, weight, sex, and cancer type in a cohort of more than 3,000 dogs: Determining the optimal age to initiate cancer screening in canine patients","volume":"18","author":"JM Rafalko","year":"2023","journal-title":"PLoS One"},{"issue":"3","key":"pcbi.1012728.ref039","article-title":"Prevalence of disorders recorded in dogs attending primary-care veterinary practices in England","volume":"9","author":"DG O Neill","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"pcbi.1012728.ref040","article-title":"Dog size and patterns of disease history across the canine age spectrum: Results from the Dog Aging Project","volume":"19","author":"Y Nam","year":"2024","journal-title":"PLoS One"},{"key":"pcbi.1012728.ref041","author":"TP Bellumori","year":"2013"},{"issue":"1","key":"pcbi.1012728.ref042","first-page":"97","article-title":"Canine otitis externa - Treatment and complications","volume":"60","author":"J Bajwa","year":"2019","journal-title":"Can Vet J"},{"key":"pcbi.1012728.ref043","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1159\/000178058","article-title":"Cushing\u2019s Disease in Dogs and Humans","volume":"71","author":"C de Bruin","year":"2009","journal-title":"Hormone Research"},{"issue":"3","key":"pcbi.1012728.ref044","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1046\/j.1463-5224.1999.00073.x","article-title":"A retrospective-cohort study on the development of cataracts in dogs with diabetes mellitus: 200 cases","volume":"2","author":"S Beam","year":"1999","journal-title":"Vet Ophthalmol"},{"issue":"1","key":"pcbi.1012728.ref045","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/jvim.15367","article-title":"Association between life span and body condition in neutered client-owned dogs","volume":"33","author":"C Salt","year":"2019","journal-title":"J Vet Intern Med"},{"key":"pcbi.1012728.ref046","author":"the DAP Consortium","year":"2023"},{"issue":"1","key":"pcbi.1012728.ref047","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12917-021-02775-3","article-title":"Prevalence of commonly diagnosed disorders in UK dogs under primary veterinary care: results and applications","volume":"17","author":"DG O\u2019Neill","year":"2021","journal-title":"BMC Vet Res"},{"issue":"6","key":"pcbi.1012728.ref048","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.kint.2021.09.016","article-title":"Role of proteinuria in the anemia of chronic kidney disease","volume":"100","author":"TB Dr\u00fceke","year":"2021","journal-title":"Kidney Int"},{"key":"pcbi.1012728.ref049","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2460\/ajvr.23.05.0097","article-title":"Anemia in canine chronic kidney disease is multifactorial and associated with decreased erythroid precursor cells, gastrointestinal bleeding, and systemic inflammation","author":"S Borin-Crivellenti","year":"2023","journal-title":"Am J Vet Res"},{"issue":"6","key":"pcbi.1012728.ref050","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.kint.2021.08.024","article-title":"Proteinuric chronic kidney disease is associated with altered red blood cell lifespan, deformability and metabolism","volume":"100","author":"R Bissinger","year":"2021","journal-title":"Kidney Int"},{"issue":"1","key":"pcbi.1012728.ref051","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1093\/jamiaopen\/ooz067","article-title":"Sensitivity of comorbidity network analysis","volume":"3","author":"JC Brunson","year":"2020","journal-title":"JAMIA Open"},{"issue":"1","key":"pcbi.1012728.ref052","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/s41467-019-08746-5","article-title":"Scale-free networks are rare","volume":"10","author":"AD Broido","year":"2019","journal-title":"Nat Commun"},{"issue":"1","key":"pcbi.1012728.ref053","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1186\/s13071-020-04343-4","article-title":"Association between lone star tick bites and increased alpha-gal sensitization: evidence from a prospective cohort of outdoor workers","volume":"13","author":"CL Mitchell","year":"2020","journal-title":"Parasit Vectors"},{"issue":"3","key":"pcbi.1012728.ref054","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3390\/vaccines7030114","article-title":"Tick Bites Induce Anti-\u03b1-Gal Antibodies in Dogs","volume":"7","author":"A Hod\u017ei\u0107","year":"2019","journal-title":"Vaccines (Basel)"},{"key":"pcbi.1012728.ref055","year":"2024"},{"key":"pcbi.1012728.ref056","first-page":"341","article-title":"Immune-mediated keratoconjunctivitis sicca in dogs: current perspectives on management","volume":"6","author":"PL Dodi","year":"2015","journal-title":"Vet Med Res Rep"},{"issue":"2","key":"pcbi.1012728.ref057","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/art.11009","article-title":"Response of joint structures to inactivity and to reloading after immobilization","volume":"49","author":"KD Brandt","year":"2003","journal-title":"Arthritis Rheum"},{"issue":"5","key":"pcbi.1012728.ref058","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/s41584-019-0202-1","article-title":"Spontaneous dog osteoarthritis - a One Medicine vision","volume":"15","author":"RL Meeson","year":"2019","journal-title":"Nat Rev Rheumatol"},{"issue":"3","key":"pcbi.1012728.ref059","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1939-1676.2004.tb02547.x","article-title":"Association of systemic hypertension with renal injury in dogs with induced renal failure","volume":"18","author":"DR Finco","year":"2004","journal-title":"J Vet Intern Med"},{"issue":"8","key":"pcbi.1012728.ref060","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/aje\/kwk075","article-title":"Evidence of a healthy volunteer effect in the prostate, lung, colorectal, and ovarian cancer screening trial","volume":"165","author":"PF Pinsky","year":"2007","journal-title":"Am J Epidemiol"},{"issue":"7","key":"pcbi.1012728.ref061","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/0895-4356(96)00009-1","article-title":"Healthy volunteer effect in a cohort study: temporal resolution in the Adventist Health Study","volume":"49","author":"KD Lindsted","year":"1996","journal-title":"J Clin Epidemiol"},{"issue":"7","key":"pcbi.1012728.ref062","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/oxfordjournals.aje.a116739","article-title":"Sample sizes for prevention trials have been too small","volume":"137","author":"F Ederer","year":"1993","journal-title":"Am J Epidemiol"},{"issue":"9","key":"pcbi.1012728.ref063","first-page":"991","article-title":"Canine pododermatitis","volume":"57","author":"J Bajwa","year":"2016","journal-title":"Can Vet J"},{"issue":"1","key":"pcbi.1012728.ref064","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/emph\/eoad011","article-title":"Social determinants of health and disease in companion dogs: a cohort study from the Dog Aging Project","volume":"11","author":"BM McCoy","year":"2023","journal-title":"Evol Med Public Health"},{"issue":"2","key":"pcbi.1012728.ref065","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.tvjl.2011.06.018","article-title":"International and collaborative strategies to enhance genetic health in purebred dogs","volume":"189","author":"\u00c5A Hedhammar","year":"2011","journal-title":"Vet J"},{"issue":"2","key":"pcbi.1012728.ref066","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/oxfordjournals.pan.a004868","article-title":"Logistic Regression in Rare Events Data","volume":"9","author":"G King","year":"2001","journal-title":"Polit Anal"},{"issue":"12","key":"pcbi.1012728.ref067","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/S0895-4356(96)00236-3","article-title":"A simulation study of the number of events per variable in logistic regression analysis","volume":"49","author":"P Peduzzi","year":"1996","journal-title":"J Clin Epidemiol"},{"key":"pcbi.1012728.ref068","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.csda.2012.10.006","article-title":"On computing the distribution function for the Poisson binomial distribution","volume":"59","author":"Y Hong","year":"2013","journal-title":"Comput Stat Data Anal"},{"key":"pcbi.1012728.ref069","author":"EB Pearson","year":"2024"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012728","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T17:25:29Z","timestamp":1755192329000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012728"}},"subtitle":[],"editor":[{"given":"Benjamin","family":"Hall","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":69,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1012728","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,14]]}}}