Abstract
Domestic dogs display a wide array of heritable behaviors that have intermediate genetic complexity thanks to a long history of human-influenced selection. Comparative genetics in dogs could address the scarcity of non-human neurogenetic systems relevant to human neuropsychiatric disorders, which are characterized by mental, emotional, and behavioral symptoms and involve vastly complex genetic and non-genetic risk factors. Our review describes the diverse behavioral “phenome” of domestic dogs, past and ongoing sources of behavioral selection, and the state of canine behavioral genetics. We highlight two naturally disordered behavioral domains that illustrate how dogs may prove useful as a comparative, forward neurogenetic system: canine age-related cognitive dysfunction, which can be examined more rapidly given the attenuated lifespan of dogs, and compulsive disorders, which may have genetic roots in purpose-bred behaviors. Growing community science initiatives aimed at the companion dog population will be well suited to investigating such complex behavioral phenotypes and offer a comparative resource that parallels human genomic initiatives in scale and dimensionality.
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References
2020 NSDUH annual national report. (2020). https://www.samhsa.gov/data/report/2020-nsduh-annual-national-report
Abey A, Davies D, Goldsbury C, Buckland M, Valenzuela M, Duncan T (2021) Distribution of tau hyperphosphorylation in canine dementia resembles early Alzheimer’s disease and other tauopathies. Brain Pathol 31(1):144–162
Alföldi J, Lindblad-Toh K (2013) Comparative genomics as a tool to understand evolution and disease. Genome Res 23(7):1063–1068
Andersson L, Georges M (2004) Domestic-animal genomics: deciphering the genetics of complex traits. Nat Rev Genet 5(3):202–212
Andics A, Gácsi M, Faragó T, Kis A, Miklósi A (2014) Voice-sensitive regions in the dog and human brain are revealed by comparative fMRI. Curr Biol CB 24(5):574–578
Andrews SJ, Das D, Cherbuin N, Anstey KJ, Easteal S (2016) Association of genetic risk factors with cognitive decline: the PATH through life project. Neurobiol Aging 41:150–158
Andrews SJ, Fulton-Howard B, Goate A (2020) Interpretation of risk loci from genome-wide association studies of Alzheimer’s disease. Lancet Neurol 19(4):326–335
Araujo JA, Greig NH, Ingram DK, Sandin J, de Rivera C, Milgram NW (2011) Cholinesterase inhibitors improve both memory and complex learning in aged beagle dogs. J Alzheimers Dis JAD 26(1):143–155
Arnold PD, Askland KD, Barlassina C, Bellodi L, Bienvenu OJ, Black D, Bloch M, Brentani H, Burton CL, Camarena B, Cappi C, Cath D, Cavallini M, Conti D, Cook E, Coric V, Cullen BA, Cusi D, Davis LK et al (2018) Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis. Mol Psychiatry 23:1181
Assary E, Vincent JP, Keers R, Pluess M (2018) Gene-environment interaction and psychiatric disorders: review and future directions. Semin Cell Dev Biol 77:133–143
Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O’Brien DP, Lindblad-Toh K, Coates JR (2009) Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 106(8):2794–2799
Bellenguez C, Küçükali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, Naj AC, Campos-Martin R, Grenier-Boley B, Andrade V, Holmans PA, Boland A, Damotte V, van der Lee SJ, Costa MR, Kuulasmaa T, Yang Q, de Rojas I, Bis JC et al (2022) New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet 54(4):412–436
Bennett PC, Rohlf VI (2007) Owner-companion dog interactions: Relationships between demographic variables, potentially problematic behaviours, training engagement and shared activities. Appl Anim Behav Sci 102(1):65–84
Bergström A, Frantz L, Schmidt R, Ersmark E, Lebrasseur O, Girdland-Flink L, Lin AT, Storå J, Sjögren K-G, Anthony D, Antipina E, Amiri S, Bar-Oz G, Bazaliiskii VI, Bulatović J, Brown D, Carmagnini A, Davy T, Fedorov S (2020) Origins and genetic legacy of prehistoric dogs. Science 370(6516):557–564
Berns GS, Brooks A, Spivak M (2013) Replicability and heterogeneity of awake unrestrained canine FMRI responses. PLoS ONE 8(12):e81698
Berns GS, Brooks AM, Spivak M (2015) Scent of the familiar: an fMRI study of canine brain responses to familiar and unfamiliar human and dog odors. Behav Proc 110:37–46
Bischkopf J, Busse A, Angermeyer MC (2002) Mild cognitive impairment—a review of prevalence, incidence and outcome according to current approaches. Acta Psychiatr Scand 106(6):403–414
Bookman EB, McAllister K, Gillanders E, Wanke K, Balshaw D, Rutter J, Reedy J, Shaughnessy D, Agurs-Collins T, Paltoo D, Atienza A, Bierut L, Kraft P, Fallin MD, Perera F, Turkheimer E, Boardman J, Marazita ML, Rappaport SM et al (2011) Gene-environment interplay in common complex diseases: forging an integrative model—recommendations from an NIH workshop. Genet Epidemiol 35(4):217–225
Border R, Athanasiadis G, Buil A, Schork AJ, Cai N, Young AI, Werge T, Flint J, Kendler KS, Sankararaman S, Dahl AW, Zaitlen NA (2022) Cross-trait assortative mating is widespread and inflates genetic correlation estimates. Science 378(6621):754–761
Bosse M, Megens H-J, Derks MFL, de Cara ÁMR, Groenen MAM (2019) Deleterious alleles in the context of domestication, inbreeding, and selection. Evol Appl 12(1):6–17
Boyko AR (2011) The domestic dog: man’s best friend in the genomic era. Genome Biol 12(2):216
Brainstorm Consortium, Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, Duncan L, Escott-Price V, Falcone GJ, Gormley P, Malik R, Patsopoulos NA, Ripke S, Wei Z, Yu D, Lee PH, Turley P, Grenier-Boley B, Chouraki V et al (2018) Analysis of shared heritability in common disorders of the brain. Science. https://doi.org/10.1126/science.aap8757
Bray EE, Otto CM, Udell MAR, Hall NJ, Johnston AM, MacLean EL (2021) Enhancing the selection and performance of working dogs. Front Vet Sci 8:644431
Brisbare-Roch C, Dingemanse J, Koberstein R, Hoever P, Aissaoui H, Flores S, Mueller C, Nayler O, van Gerven J, de Haas SL, Hess P, Qiu C, Buchmann S, Scherz M, Weller T, Fischli W, Clozel M, Jenck F (2007) Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med 13(2):150–155
Browne HA, Gair SL, Scharf JM, Grice DE (2014) Genetics of obsessive-compulsive disorder and related disorders. Psychiatr Clin N Am 37(3):319–335
Caius J (1576) Of Englishe dogges, the diversities, the names, the natures, and the properties. In: Fleming A(ed) De Capo, Boston
Cervin M, McNeel MM, Wilhelm S, McGuire JF, Murphy TK, Small BJ, Geller DA, Storch EA (2022a) Cognitive beliefs across the symptom dimensions of pediatric obsessive-compulsive disorder: type of symptom matters. Behav Ther 53(2):240–254
Cervin M, Miguel EC, Güler AS, Ferrão YA, Erdoğdu AB, Lazaro L, Gökçe S, Geller DA, Yulaf Y, Başgül ŞS, Özcan Ö, Karabekiroğlu K, Fontenelle LF, Yazgan Y, Storch EA, Leckman JF, do RosárioMataix-Cols MCM (2022b) Towards a definitive symptom structure of obsessive-compulsive disorder: a factor and network analysis of 87 distinct symptoms in 1366 individuals. Psychol Med 52(14):3267–3279
Chapagain D, Range F, Huber L, Virányi Z (2018) Cognitive aging in dogs. Gerontology 64(2):165–171
Chen FL, Zimmermann M, Hekman JP, Lord KA, Logan B, Russenberger J, Leighton EA, Karlsson EK (2021) Advancing genetic selection and behavioral genomics of working dogs through collaborative science. Front Vet Sci. https://doi.org/10.3389/fvets.2021.662429
Chiou KL, DeCasien AR, Rees KP, Testard C, Spurrell CH, Gogate AA, Pliner HA, Tremblay S, Mercer A, Whalen CJ, Negrón-Del Valle JE, Janiak MC, Bauman Surratt SE, González O, Compo NR, Stock MK, Ruiz-Lambides AV, Martínez MI, Cayo Biobank Research Unit et al (2022) Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment. Nat Neurosci 25(12):1714–1723
Clay L, Paterson MBA, Bennett P, Perry G, Phillips CCJ (2020) Do behaviour assessments in a shelter predict the behaviour of dogs post-adoption? Anim Open Access J MDPI 10(7):1225. https://doi.org/10.3390/ani10071225
Coppinger R, Coppinger L (2002) Dogs: a new understanding of canine origin, behavior and evolution. University of Chicago Press, Chicago
Court MH (2013) Canine cytochrome P-450 pharmacogenetics. Vet Clin N Am Small Anim Pract 43(5):1027–1038
Creevy KE, Akey JM, Kaeberlein M, Promislow DEL, Dog Aging Project Consortium (2022) An open science study of ageing in companion dogs. Nature 602(7895):51–57
Cross-Disorder Group of the Psychiatric Genomics Consortium (2019) Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders. Cell 179(7):1469-1482.e11
Cummings BJ, Head E, Ruehl W, Milgram NW, Cotman CW (1996) The canine as an animal model of human aging and dementia. Neurobiol Aging 17(2):259–268
Cummings J, Aisen PS, DuBois B, Frölich L, Jack CR Jr, Jones RW, Morris JC, Raskin J, Dowsett SA, Scheltens P (2016) Drug development in Alzheimer’s disease: the path to 2025. Alzheimers Res Therapy 8:39
Cummings J, Reiber C, Kumar P (2018) The price of progress: funding and financing Alzheimer’s disease drug development. Alzheimers Dement J Alzheimers Assoc 4:330–343
Cummings J, Lee G, Nahed P, Kambar MEZN, Zhong K, Fonseca J, Taghva K (2022) Alzheimer’s disease drug development pipeline: 2022. Alzheimers Dement J Alzheimers Assoc 8(1):e12295
Davis LK, Yu D, Keenan CL, Gamazon ER, Konkashbaev AI, Derks EM, Neale BM, Yang J, Lee SH, Evans P, Barr CL, Bellodi L, Benarroch F, Berrio GB, Bienvenu OJ, Bloch MH, Blom RM, Bruun RD, Budman CL et al (2013) Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genet 9(10):e1003864
DeBoever C, Tanigawa Y, Aguirre M, McInnes G, Lavertu A, Rivas MA (2020) Assessing digital phenotyping to enhance genetic studies of human diseases. Am J Hum Genet 106(5):611–622
Dewey CW, Davies ES, Xie H, Wakshlag JJ (2019) Canine cognitive dysfunction: pathophysiology, diagnosis, and treatment. Vet Clin N Am Small Ani Pract 49(3):477–499
Dinwoodie IR, Dwyer B, Zottola V, Gleason D, Dodman NH (2019) Demographics and comorbidity of behavior problems in dogs. J Vet Behav Clin Appl Res off J Austr Vet Behav Interest Group Int Work Dog Breed Assoc 32:62–71
Dutrow EV, Serpell JA, Ostrander EA (2022) Domestic dog lineages reveal genetic drivers of behavioral diversification. Cell 185(25):4737-4755.e18
Elgier AM, Jakovcevic A, Barrera G, Mustaca AE, Bentosela M (2009) Communication between domestic dogs (Canis familiaris) and humans: dogs are good learners. Behav Proc 81(3):402–408
Eyre AW, Zapata I, Hare E, Lee KMN, Bellis C, Essler JL, Otto CM, Serpell JA, Alvarez CE (2022) Genome scanning of behavioral selection in a canine olfactory detection breeding cohort. Sci Rep 12(1):14984
Fan CC, Bartsch H, Schork AJ, Chen C-H, Wang Y, Lo M-T, Brown TT, Kuperman JM, Hagler DJ Jr, Schork NJ, Jernigan TL, Dale AM, Pediatric Imaging, Neurocognition, and Genetics Study (2015) Modeling the 3D geometry of the cortical surface with genetic ancestry. Curr Biol CB 25(15):1988–1992
Ferres K, Schloesser T, Gloor PA (2022) Predicting dog emotions based on posture analysis using DeepLabCut. Future Internet 14(4):97
Floris M, Olla S, Schlessinger D, Cucca F (2018) Genetic-driven druggable target identification and validation. Trends Genet TIG 34(7):558–570
Fratkin JL, Sinn DL, Patall EA, Gosling SD (2013) Personality consistency in dogs: a meta-analysis. PLoS ONE 8(1):e54907
Friedrich J, Talenti A, Arvelius P, Strandberg E, Haskell MJ, Wiener P (2020) Unravelling selection signatures in a single dog breed suggests recent selection for morphological and behavioral traits. Adv Genet 1(1):e10024
GBD 2019 Dementia Forecasting Collaborators (2022) Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health 7(2):e105–e125
Gnanadesikan GE, Hare B, Snyder-Mackler N, Call J, Kaminski J, Miklósi Á, MacLean EL (2020) Breed differences in dog cognition associated with brain-expressed genes and neurological functions. Integr Comp Biol 60(4):976–990
GNT Pharma’s GedaCure® Approved for the Treatment of Dogs With Cognitive Dysfunction Syndrome (2021). https://www.businesswire.com/news/home/20210210005036/en/GNT-Pharma%E2%80%99s-GedaCure%C2%AE-Approved-for-the-Treatment-of-Dogs-With-Cognitive-Dysfunction-Syndrome
Gosling SD (2008) Personality in non-human animals. Soc Pers Psychol Compass 2(2):985–1001
Head E (2013) A canine model of human aging and Alzheimer’s disease. Biochem Biophys Acta 1832(9):1384–1389
Hecht EE, Smaers JB, Dunn WD, Kent M, Preuss TM, Gutman DA (2019) Significant neuroanatomical variation among domestic dog breeds. J Neurosci off J Soc Neurosci 39(39):7748–7758
Hecht EE, Zapata I, Alvarez CE, Gutman DA, Preuss TM, Kent M, Serpell JA (2021) Neurodevelopmental scaling is a major driver of brain-behavior differences in temperament across dog breeds. Brain Struct Funct 226(8):2725–2739
Hoel JA, Templeton GB, Fefer G, Case BC, Shah A, Gruen ME, Olby NJ (2021) Sustained gaze is a reliable in-home test of attention for aging pet dogs. Front Vet Sci 8:819135
Hsu Y, Serpell JA (2003) Development and validation of a questionnaire for measuring behavior and temperament traits in pet dogs. J Am Vet Med Assoc. https://avmajournals.avma.org/view/journals/javma/223/9/javma.2003.223.1293.xml
Huang TH, Loughnan R, Thompson WK, Fan CC (2022) The impact of population stratification on the analysis of multimodal neuroimaging derived measures. bioRxiv. https://doi.org/10.1101/2022.08.06.503037
Hülsmeyer V-I, Fischer A, Mandigers PJJ, DeRisio L, Berendt M, Rusbridge C, Bhatti SFM, Pakozdy A, Patterson EE, Platt S, Packer RMA, Volk HA (2015) International Veterinary Epilepsy Task Force’s current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs. BMC Vet Res 11:175
HumphreyE, Warner LH (1934) Working dogs: an attempt to produce a strain of german shepherds which combines working ability and beauty of conformation, by Elliott Humphrey and Lubien Warner; with a Foreword by Raymond Pearl
Hyde CL, Nagle MW, Tian C, Chen X, Paciga SA, Wendland JR, Tung JY, Hinds DA, Perlis RH, Winslow AR (2016) Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nat Genet 48(9):1031–1036
Ilska J, Haskell MJ, Blott SC, Sánchez-Molano E, Polgar Z, Lofgren SE, Clements DN, Wiener P (2017) Genetic characterization of dog personality traits. Genetics 206(2):1101–1111
Ivansson EL, Megquier K, Kozyrev SV, Murén E, Körberg IB, Swofford R, Koltookian M, Tonomura N, Zeng R, Kolicheski AL, Hansen L, Katz ML, Johnson GC, Johnson GS, Coates JR, Lindblad-Toh K (2016) Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy. Proc Natl Acad Sci USA 113(22):E3091–E3100
Jones AC (2008) Development and validation of a dog personality questionnaire. University of Texas, Austin
Junttila S, Valros A, Mäki K, Väätäjä H, Reunanen E, Tiira K (2022) Breed differences in social cognition, inhibitory control, and spatial problem-solving ability in the domestic dog (Canis familiaris). Sci Rep 12(1):1–15
Kabadayi C, Bobrowicz K, Osvath M (2018) The detour paradigm in animal cognition. Anim Cogn 21(1):21–35
Karamperis K, Koromina M, Papantoniou P, Skokou M, Kanellakis F, Mitropoulos K, Vozikis A, Müller DJ, Patrinos GP, Mitropoulou C (2021) Economic evaluation in psychiatric pharmacogenomics: a systematic review. Pharmacogenom J 21(4):533–541
Karl S, Boch M, Zamansky A, van der Linden D, Wagner IC, Völter CJ, Lamm C, Huber L (2020) Exploring the dog-human relationship by combining fMRI, eye-tracking and behavioural measures. Sci Rep 10(1):22273
Kawas C, Gray S, Brookmeyer R, Fozard J, Zonderman A (2000) Age-specific incidence rates of Alzheimer’s disease: the Baltimore longitudinal study of aging. Neurology 54(11):2072–2077
Kongara K (2018) Pharmacogenetics of opioid analgesics in dogs. J Vet Pharmacol Ther 41(2):195–204. https://doi.org/10.1111/jvp.12452
Kubinyi E, Gosling SD, Miklósi Á (2015) A comparison of rating and coding behavioural traits in dogs. Acta Biol Hung 66(1):27–40
Landsberg GM, Nichol J, Araujo JA (2012) Cognitive dysfunction syndrome: a disease of canine and feline brain aging. Vet Clin N Am Small Anim Practi 42(4):749–768 (vii)
Lauer J, Zhou M, Ye S, Menegas W, Schneider S, Nath T, Rahman MM, Di Santo V, Soberanes D, Feng G, Murthy VN, Lauder G, Dulac C, Mathis MW, Mathis A (2022) Multi-animal pose estimation, identification and tracking with DeepLabCut. Nat Methods 19(4):496–504
Lavan RP (2013) Development and validation of a survey for quality of life assessment by owners of healthy dogs. Vet J 197(3):578–582
Lazzaroni M, Marshall-Pescini S, Manzenreiter H, Gosch S, Přibilová L, Darc L, McGetrick J, Range F (2020) Why do dogs look back at the human in an impossible task? Looking back behaviour may be over-interpreted. Anim Cogn 23(3):427–441
Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, 23andMe Research Team, Million Veteran Program, Concato J, Polimanti R, Gelernter J (2021) Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nat Neurosci 24(7):954–963
Lill CM, Bertram L (2022) Genome-wide analysis furthers decoding of Alzheimer disease genetics [Review of Genome-wide analysis furthers decoding of Alzheimer disease genetics]. Nat Rev Neurol 18(7):387–388
Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98(3):365–376
Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, Clamp M, Chang JL, Kulbokas EJ 3rd, Zody MC, Mauceli E, Xie X, Breen M, Wayne RK, Ostrander EA, Ponting CP, Galibert F, Smith DR, DeJong PJ et al (2005) Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438(7069):803–819
Lord K, Feinstein M, Smith B, Coppinger R (2013) Variation in reproductive traits of members of the genus Canis with special attention to the domestic dog (Canis familiaris). Behav Proc 92:131–142
Lorenz K (1981) The foundations of ethology. Springer Nature, Berlin
Luescher AU (2003) Diagnosis and management of compulsive disorders in dogs and cats. Vet Clin N Am Small Anim Pract 33(2):253–267 (vi)
Luigjes J, Lorenzetti V, de Haan S, Youssef GJ, Murawski C, Sjoerds Z, van den Brink W, Denys D, Fontenelle LF, Yücel M (2019) Defining compulsive behavior. Neuropsychol Rev 29(1):4–13
MacLean EL, Snyder-Mackler N, von Holdt BM, Serpell JA (2019) Highly heritable and functionally relevant breed differences in dog behaviour. Proc Biol Sci R Soc 286(1912):20190716
Madari A, Farbakova J, Katina S, Smolek T, Novak P, Weissova T, Novak M, Zilka N (2015) Assessment of severity and progression of canine cognitive dysfunction syndrome using the CAnine DEmentia Scale (CADES). Appl Anim Behav Sci 171:138–145
Majumder SS, Bhadra A, Ghosh A, Mitra S, Bhattacharjee D, Chatterjee J, Nandi AK, Bhadra A (2014) To be or not to be social: foraging associations of free-ranging dogs in an urban ecosystem. Acta Ethol 17(1):1–8
Marsden CD, Ortega-Del Vecchyo D, O’Brien DP, Taylor JF, Ramirez O, Vilà C, Marques-Bonet T, Schnabel RD, Wayne RK, Lohmueller KE (2016) Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs. Proc Natl Acad Sci USA 113(1):152–157
Martinez SE, Andresen MC, Zhu Z, Papageorgiou I, Court MH (2020) Pharmacogenomics of poor drug metabolism in greyhounds: cytochrome P450 (CYP) 2B11 genetic variation, breed distribution, and functional characterization. Sci Rep 10(1):1–19
Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL (2015) Alzheimer’s disease. Nat Rev Dis Prim 1:15056
Mataix-Cols D, Hansen B, Mattheisen M, Karlsson EK, Addington AM, Boberg J, Djurfeldt DR, Halvorsen M, Lichtenstein P, Solem S, Lindblad-Toh K, Nordic OCD and Related Disorders Consortium (NORDiC), Haavik J, Kvale G, Rück C, Crowley JJ (2020) Nordic OCD & Related Disorders Consortium: Rationale, design, and methods. Am J Med Genet Part B Neuropsychiatr Genet off Publ Int Soc Psychiatr Genet 183(1):38–50
Mattheisen M, Samuels JF, Wang Y, Greenberg BD, Fyer AJ, McCracken JT, Geller DA, Murphy DL, Knowles JA, Grados MA, Riddle MA, Rasmussen SA, McLaughlin NC, Nurmi EL, Askland KD, Qin H-D, Cullen BA, Piacentini J, Pauls DL et al (2015) Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS. Mol Psychiatry 20(3):337–344
Mazzorin JDG, Tagliacozzo A (1997) Dog remains in Italy from the Neolithic to the Roman period. Anthropozoologica 25:429
Mazzorin JDG, Tagliacozzo A (2000) Morphological and osteological changes in the dog from the Neolithic to the Roman period in Italy. Dogs through time: an archaeological perspective. Archaeopress, Oxford, pp 141–161
Mealey KL, Meurs KM (2008) Breed distribution of the ABCB1-1Delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping. J Am Vet Med Assoc 233(6):921–924
Merikangas KR, He J-P, Burstein M, Swanson SA, Avenevoli S, Cui L, Benjet C, Georgiades K, Swendsen J (2010) Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A). J Am Acad Child Adolesc Psychiatry 49(10):980–989
Milne ME, Steward C, Firestone SM, Long SN, O’Brien TJ, Moffat BA (2016) Development of representative magnetic resonance imaging-based atlases of the canine brain and evaluation of three methods for atlas-based segmentation. Am J Vet Res 77(4):395–403
Mirkó E, Kubinyi E, Gácsi M, Miklósi Á (2012) Preliminary analysis of an adjective-based dog personality questionnaire developed to measure some aspects of personality in the domestic dog (Canis familiaris). Appl Anim Behav Sci 138(1):88–98
Moon-Fanelli AA, Dodman NH, Famula TR, Cottam N (2011) Characteristics of compulsive tail chasing and associated risk factors in Bull Terriers. J Am Vet Med Assoc 238(7):883–889
Morrill K, Hekman J, Li X, McClure J, Logan B, Goodman L, Gao M, Dong Y, Alonso M, Carmichael E, Snyder-Mackler N, Alonso J, Noh HJ, Johnson J, Koltookian M, Lieu C, Megquier K, Swofford R, Turner-Maier J et al (2022) Ancestry-inclusive dog genomics challenges popular breed stereotypes. Science 376(6592):eabk0639
Morris GP, Clark IA, Vissel B (2014) Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer’s disease. Acta Neuropathol Commun 2:135
Morris J, Bailey MES, Baldassarre D, Cullen B, de Faire U, Ferguson A, Gigante B, Giral P, Goel A, Graham N, Hamsten A, Humphries SE, Johnston KJA, Lyall DM, Lyall LM, Sennblad B, Silveira A, Smit AJ, Tremoli E et al (2019) Genetic variation in CADM2 as a link between psychological traits and obesity. Sci Rep 9(1):7339
Murray GK, Lin T, Austin J, McGrath JJ, Hickie IB, Wray NR (2021) Could polygenic risk scores be useful in psychiatry?: A review. JAMA Psychiat 78(2):210–219
Nazeer A, Latif F, Mondal A, Azeem MW, Greydanus DE (2020) Obsessive-compulsive disorder in children and adolescents: epidemiology, diagnosis and management. Transl Pediatr 9(Suppl 1):S76–S93
Neff MW, Robertson KR, Wong AK, Safra N, Broman KW, Slatkin M, Mealey KL, Pedersen NC (2004) Breed distribution and history of canine mdr1-1Delta, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage. Proc Natl Acad Sci USA 101(32):11725–11730
Nestler EJ, Hyman SE (2010) Animal models of neuropsychiatric disorders. Nat Neurosci 13(10):1161–1169
Nitzsche B, Boltze J, Ludewig E, Flegel T, Schmidt MJ, Seeger J, Barthel H, Brooks OW, Gounis MJ, Stoffel MH, Schulze S (2019) A stereotaxic breed-averaged, symmetric T2w canine brain atlas including detailed morphological and volumetrical data sets. Neuroimage 187:93–103
Noh HJ, Tang R, Flannick J, O’Dushlaine C, Swofford R, Howrigan D, Genereux DP, Johnson J, van Grootheest G, Grünblatt E, Andersson E, Djurfeldt DR, Patel PD, Koltookian M, Hultman CM, Pato MT, Pato CN, Rasmussen SA, Jenike MA et al (2017) Integrating evolutionary and regulatory information with a multispecies approach implicates genes and pathways in obsessive-compulsive disorder. Nat Commun 8(1):774
NOT-MH-19-053: notice of NIMHs considerations regarding the use of animal neurobehavioral approaches in basic and pre-clinical studies. (n.d.). https://grants.nih.gov/grants/guide/notice-files/NOT-MH-19-053.html. Accessed 18 Dec 2022
O’Neill DG, Coulson NR, Church DB, Brodbelt DC (2017) Demography and disorders of German Shepherd Dogs under primary veterinary care in the UK. Canine Genet Epidemiol 4:7
Ortolani A, Vernooij H, Coppinger R (2009) Ethiopian village dogs: behavioural responses to a stranger’s approach. Appl Anim Behav Sci 119(3):210–218
Ostrander EA, Wang G-D, Larson G, vonHoldt BM, Davis BW, Jagannathan V, Hitte C, Wayne RK, Zhang Y-P, Dog10K Consortium (2019) Dog10K: an international sequencing effort to advance studies of canine domestication, phenotypes and health. Natl Sci Rev 6(4):810–824
Overall KL (2000) Natural animal models of human psychiatric conditions: assessment of mechanism and validity. Prog Neuropsychopharmacol Biol Psychiatry 24(5):727–776
Overall KL (2019) Evidence-based paradigm shifts in veterinary behavioral medicine. J Am Vet Med Assoc 254(7):798–807
Panek WK, Gruen ME, Murdoch DM, Marek RD, Stachel AF, Mowat FM, Saker KE, Olby NJ (2020) Plasma neurofilament light chain as a translational biomarker of aging and neurodegeneration in dogs. Mol Neurobiol 57(7):3143–3149
Patronek GJ, Bradley J (2016) No better than flipping a coin: reconsidering canine behavior evaluations in animal shelters. J Vet Behav Clin Appl Res off J Austr Vet Behav Interest Group Int Work Dog Breed Assoc 15:66–77
Pitul’ko VV, Kasparov AK (1996) Ancient arctic hunters: material culture and survival strategy. Arct Anthropol 33(1):1–36
Pitulko VV, Kasparov AK (2017) Archaeological dogs from the Early Holocene Zhokhov site in the Eastern Siberian Arctic. J Archaeol Sci Rep 13:491–515
Plassais J, Kim J, Davis BW, Karyadi DM, Hogan AN, Harris AC, Decker B, Parker HG, Ostrander EA (2019) Whole genome sequencing of canids reveals genomic regions under selection and variants influencing morphology. Nat Commun 10(1):1489
Prichard A, Chhibber R, King J, Athanassiades K, Spivak M, Berns GS (2020) Decoding odor mixtures in the dog brain: an awake fMRI study. Chem Senses 45(9):833–844
Raffan E, Smith SP, O’Rahilly S, Wardle J (2015) Development, factor structure and application of the Dog Obesity Risk and Appetite (DORA) questionnaire. PeerJ 3:e1278
Raffan E, Dennis RJ, O’Donovan CJ, Becker JM, Scott RA, Smith SP, Withers DJ, Wood CJ, Conci E, Clements DN, Summers KM, German AJ, Mellersh CS, Arendt ML, Iyemere VP, Withers E, Söder J, Wernersson S, Andersson G et al (2016) A deletion in the canine POMC gene is associated with weight and appetite in obesity-prone labrador retriever dogs. Cell Metab 23(5):893–900
Rotroff DM, Thomas R, Breen M, Motsinger-Reif AA (2013) Naturally occuring canine cancers: powerful models for stimulating pharmacogenomic advancement in human medicine. Pharmacogenomics 14(16):1929–1931
Rowan TN, Durbin HJ, Seabury CM, Schnabel RD, Decker JE (2021) Powerful detection of polygenic selection and evidence of environmental adaptation in US beef cattle. PLoS Genet 17(7):e1009652
Ruple A, MacLean E, Snyder-Mackler N, Creevy KE, Promislow D (2022) Dog models of aging. Ann Rev Anim Biosci 10:419–439
Salonen M, Sulkama S, Mikkola S, Puurunen J, Hakanen E, Tiira K, Araujo C, Lohi H (2020) Prevalence, comorbidity, and breed differences in canine anxiety in 13,700 Finnish pet dogs. Sci Rep 10(1):2962
Salonen M, Mikkola S, Hakanen E, Sulkama S, Puurunen J, Lohi H (2021) Reliability and validity of a dog personality and unwanted behavior survey. Anim Open Access J MDPI 11(5):1234. https://doi.org/10.3390/ani11051234
Salvin HE, McGreevy PD, Sachdev PS, Valenzuela MJ (2011) The canine cognitive dysfunction rating scale (CCDR): a data-driven and ecologically relevant assessment tool. Vet J 188(3):331–336
Sanchez-Roige S, Palmer AA, Fontanillas P, Elson SL, 23andMe Research Team, the Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, Adams MJ, Howard DM, Edenberg HJ, Davies G, Crist RC, Deary IJ, McIntosh AM, Clarke T-K (2019) Genome-wide association study meta-analysis of the alcohol use disorders identification test (AUDIT) in two population-based cohorts. Am J Psychiatry 176(2):107–118
Sarkar R, Sau S, Bhadra A (2019) Scavengers can be choosers: a study on food preference in free-ranging dogs. Appl Anim Behav Sci 216:38–44
Schachter AS, Davis KL (2000) Alzheimer’s disease. Dialogues Clin Neurosci 2(2):91–100
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511(7510):421–427
Schmidt F, Boltze J, Jäger C, Hofmann S, Willems N, Seeger J, Härtig W, Stolzing A (2015) Detection and quantification of β-amyloid, pyroglutamyl Aβ, and tau in aged canines. J Neuropathol Exp Neurol 74(9):912–923
Schoenebeck JJ, Ostrander EA (2013) The genetics of canine skull shape variation. Genetics 193(2):317–325
Schönknecht P, Pantel J, Kruse A, Schröder J (2005) Prevalence and natural course of aging-associated cognitive decline in a population-based sample of young-old subjects. Am J Psychiatry 162(11):2071–2077
Schütt T, Toft N, Berendt M (2015) Cognitive function, progression of age-related behavioral changes, biomarkers, and survival in dogs more than 8 years old. J Vet Intern Med Am Coll Vet Intern Med 29(6):1569–1577
Schütt T, Helboe L, Pedersen LØ, Waldemar G, Berendt M, Pedersen JT (2016) Dogs with cognitive dysfunction as a spontaneous model for early Alzheimer’s disease: a translational study of neuropathological and inflammatory markers. J Alzheimer’s Di JAD 52(2):433–449
Scott JP, Fuller JL (1965) Genetics and the social behavior of the dog. University of Chicago Press, Chicago
Simpson BS, Papich MG (2003) Pharmacologic management in veterinary behavioral medicine. Vet Clin N Am Small Anim Pract 33(2):365–404 (vii)
Sinding M-HS, Gopalakrishnan S, Ramos-Madrigal J, de Manuel M, Pitulko VV, Kuderna L, Feuerborn TR, Frantz LAF, Vieira FG, Niemann J, Samaniego Castruita JA, Carøe C, Andersen-Ranberg EU, Jordan PD, Pavlova EY, Nikolskiy PA, Kasparov AK, Ivanova VV, Willerslev E et al (2020) Arctic-adapted dogs emerged at the Pleistocene–Holocene transition. Science 368(6498):1495–1499
Sinn L (2018) Advances in behavioral psychopharmacology. Vet Clin N Am Small Anim Pract 48(3):457–471
Spady TC, Ostrander EA (2008) Canine behavioral genetics: pointing out the phenotypes and herding up the genes. Am J Hum Genet 82(1):10–18
Stellato AC, Flint HE, Widowski TM, Serpell JA, Niel L (2017) Assessment of fear-related behaviours displayed by companion dogs (Canis familiaris) in response to social and non-social stimuli. Appl Anim Behav Sci 188:84–90
Stewart SE, Yu D, Scharf JM, Neale BM, Fagerness JA, Mathews CA, Arnold PD, Evans PD, Gamazon ER, Davis LK, Osiecki L, McGrath L, Haddad S, Crane J, Hezel D, Illman C, Mayerfeld C, Konkashbaev A, Liu C et al (2013) Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry 18(7):788–798
Stewart L, MacLean EL, Ivy D, Woods V, Cohen E, Rodriguez K, McIntyre M, Mukherjee S, Call J, Kaminski J, Miklósi Á, Wrangham RW, Hare B (2015) Citizen science as a new tool in dog cognition research. PLoS ONE 10(9):e0135176
Strom NI, Yu D, Gerring ZF, Halvorsen MW, Abdellaoui A, Rodriguez-Fontenla C, Sealock JM, Bigdeli T, Coleman JRI, Mahjani B, Thorp JG, Bey K, Burton CL, Luykx JJ, Zai G, Askland KD, Barlassina C, Nissen JB, Bellodi L et al (2021) Genome-wide association study identifies new locus associated with OCD. bioRxiv. https://doi.org/10.1101/2021.10.13.21261078
Studzinski CM, Araujo JA, Milgram NW (2005) The canine model of human cognitive aging and dementia: pharmacological validity of the model for assessment of human cognitive-enhancing drugs. Prog Neuropsychopharmacol Biol Psychiatry 29(3):489–498
Sullivan PF, Daly MJ, O’Donovan M (2012) Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat Rev Genet 13(8):537–551
Sullivan PF, Agrawal A, Bulik CM, Andreassen OA, Børglum AD, Breen G, Cichon S, Edenberg HJ, Faraone SV, Gelernter J, Mathews CA, Nievergelt CM, Smoller JW, O’Donovan MC, Psychiatric Genomics Consortium (2018) Psychiatric genomics: an update and an agenda. Am J Psychiatry 175(1):15–27
Sutter NB, Ostrander EA (2004) Dog star rising: the canine genetic system. Nat Rev Genet 5(12):900–910
Tapp PD, Siwak CT, Estrada J, Holowachuk D, Milgram NW (2003) Effects of age on measures of complex working memory span in the beagle dog (Canis familiaris) using two versions of a spatial list learning paradigm. Learn Mem 10(2):148–160
Teng KT-Y, Brodbelt DC, Pegram C, Church DB, O’Neill DG (2022) Life tables of annual life expectancy and mortality for companion dogs in the United Kingdom. Sci Rep 12(1):6415
Tiira K, Lohi H (2014) Reliability and validity of a questionnaire survey in canine anxiety research. Appl Anim Behav Sci 155:82–92
Uher R, Zwicker A (2017) Etiology in psychiatry: embracing the reality of poly-gene-environmental causation of mental illness. World Psychiatry off J World Psychiatr Assoc 16(2):121–129
Ward ET, Kostick KM, Lázaro-Muñoz G (2019) Integrating genomics into psychiatric practice: ethical and legal challenges for clinicians. Harv Rev Psychiatry 27(1):53–64
Watowich MM, MacLean EL, Hare B, Call J, Kaminski J, Miklósi Á, Snyder-Mackler N (2020) Age influences domestic dog cognitive performance independent of average breed lifespan. Anim Cogn 23(4):795–805
Worboys M, Strange J-M, Pemberton N (2018) The invention of the modern dog: breed and blood in Victorian Britain. JHU Press, Baltimore
Yamazaki Y, Zhao N, Caulfield TR, Liu C-C, Bu G (2019) Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat Rev Neurol 15(9):501–518
Yarborough S, Fitzpatrick A, Schwartz SM, Dog Aging Project Consortium (2022) Evaluation of cognitive function in the Dog Aging Project: associations with baseline canine characteristics. Sc Rep 12(1):13316
Zhan S, Zhang W, Niitepõld K, Hsu J, Haeger JF, Zalucki MP, Altizer S, de Roode JC, Reppert SM, Kronforst MR (2014) The genetics of monarch butterfly migration and warning colouration. Nature 514(7522):317–321
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Morrill, K., Chen, F. & Karlsson, E. Comparative neurogenetics of dog behavior complements efforts towards human neuropsychiatric genetics. Hum. Genet. 142, 1231–1246 (2023). https://doi.org/10.1007/s00439-023-02580-y
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DOI: https://doi.org/10.1007/s00439-023-02580-y