Two Novel Genomic Regions Associated with Fearfulness in Dogs Overlap Human Neuropsychiatric Loci

Overview

Journal Transl Psychiatry

Specialties Psychiatry
Public Health

Date 2019 Jan 19

PMID 30655508

Citations 15

Authors

R Sarviaho

O Hakosalo

K Tiira

S Sulkama

E Salmela

M K Hytonen

M J Sillanpaa

H Lohi

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Altered microbiome and metabolome profiling in fearful companion dogs: An exploratory study.

Sacchettino L, Costanzo M, Veneruso I, DArgenio V, Mayer M, Napolitano F PLoS One. 2025; 20(1):e0315374.

PMID: 39813205 PMC: 11734960. DOI: 10.1371/journal.pone.0315374.

Heritability and Genome-Wide Association Study of Dog Behavioral Phenotypes in a Commercial Breeding Cohort.

Bhowmik N, Cook S, Croney C, Barnard S, Romaniuk A, Ekenstedt K Genes (Basel). 2025; 15(12.

PMID: 39766878 PMC: 11675989. DOI: 10.3390/genes15121611.

Therapy and Prevention of Noise Fears in Dogs-A Review of the Current Evidence for Practitioners.

Riemer S Animals (Basel). 2023; 13(23).

PMID: 38067015 PMC: 10705068. DOI: 10.3390/ani13233664.

Modulation of dog-owner relationship and dog social and cognitive behavior by owner temperament and dog breed group.

Kujala M, Imponen N, Pirkkala A, Silfverberg T, Parviainen T, Tiira K Sci Rep. 2023; 13(1):14739.

PMID: 37679427 PMC: 10484941. DOI: 10.1038/s41598-023-41849-0.

Genomic analysis of firework fear and noise reactivity in standard poodles.

Handegard K, Storengen L, Joergensen D, Lingaas F Canine Med Genet. 2023; 10(1):2.

PMID: 36890545 PMC: 9996964. DOI: 10.1186/s40575-023-00125-0.

References

Kirsch P . Oxytocin in the socioemotional brain: implications for psychiatric disorders. Dialogues Clin Neurosci. 2016; 17(4):463-76. PMC: 4734884. View

Meerabux J, Ohba H, Iwayama Y, Maekawa M, Detera-Wadleigh S, DeLisi L . Analysis of a t(18;21)(p11.1;p11.1) translocation in a family with schizophrenia. J Hum Genet. 2009; 54(7):386-91. DOI: 10.1038/jhg.2009.47. View

Cavanna A, Seri S . Misophonia: current perspectives. Neuropsychiatr Dis Treat. 2015; 11:2117-23. PMC: 4547634. DOI: 10.2147/NDT.S81438. View

Tiira K, Hakosalo O, Kareinen L, Thomas A, Hielm-Bjorkman A, Escriou C . Environmental effects on compulsive tail chasing in dogs. PLoS One. 2012; 7(7):e41684. PMC: 3406045. DOI: 10.1371/journal.pone.0041684. View

Gee C, Peterlik D, Neuhauser C, Bouhelal R, Kaupmann K, Laue G . Blocking metabotropic glutamate receptor subtype 7 (mGlu7) via the Venus flytrap domain (VFTD) inhibits amygdala plasticity, stress, and anxiety-related behavior. J Biol Chem. 2014; 289(16):10975-10987. PMC: 4036238. DOI: 10.1074/jbc.M113.542654. View

Overall K . Natural animal models of human psychiatric conditions: assessment of mechanism and validity. Prog Neuropsychopharmacol Biol Psychiatry. 2001; 24(5):727-76. DOI: 10.1016/s0278-5846(00)00104-4. View

Thompson R, Parker K, Hallmayer J, Waugh C, Gotlib I . Oxytocin receptor gene polymorphism (rs2254298) interacts with familial risk for psychopathology to predict symptoms of depression and anxiety in adolescent girls. Psychoneuroendocrinology. 2010; 36(1):144-7. PMC: 2997902. DOI: 10.1016/j.psyneuen.2010.07.003. View

Lohoff F, Weller A, Bloch P, Nall A, Ferraro T, Berrettini W . Association between polymorphisms in the vesicle-associated membrane protein-associated protein A (VAPA) gene on chromosome 18p and bipolar disorder. J Neural Transm (Vienna). 2008; 115(9):1339-45. DOI: 10.1007/s00702-008-0093-9. View

Cosoff S, Hafner R . The prevalence of comorbid anxiety in schizophrenia, schizoaffective disorder and bipolar disorder. Aust N Z J Psychiatry. 1998; 32(1):67-72. DOI: 10.3109/00048679809062708. View

10.

Karkkainen H, Sillanpaa M . Fast genomic predictions via Bayesian G-BLUP and multilocus models of threshold traits including censored Gaussian data. G3 (Bethesda). 2013; 3(9):1511-23. PMC: 3755911. DOI: 10.1534/g3.113.007096. View

11.

Buttner A . Neurobiological underpinnings of dogs' human-like social competence: How interactions between stress response systems and oxytocin mediate dogs' social skills. Neurosci Biobehav Rev. 2016; 71:198-214. DOI: 10.1016/j.neubiorev.2016.08.029. View

12.

Wilbe M, Ziener M, Aronsson A, Harlos C, Sundberg K, Norberg E . DLA class II alleles are associated with risk for canine symmetrical lupoid onychodystrophy [corrected](SLO). PLoS One. 2010; 5(8):e12332. PMC: 2925901. DOI: 10.1371/journal.pone.0012332. View

13.

Alliey-Rodriguez N, Zhang D, Badner J, Lahey B, Zhang X, Dinwiddie S . Genome-wide association study of personality traits in bipolar patients. Psychiatr Genet. 2011; 21(4):190-4. PMC: 3125400. DOI: 10.1097/YPG.0b013e3283457a31. View

14.

Tiira K, Lohi H . Early Life Experiences and Exercise Associate with Canine Anxieties. PLoS One. 2015; 10(11):e0141907. PMC: 4631323. DOI: 10.1371/journal.pone.0141907. View

15.

Manohar S, Spoth J, Radziwon K, Auerbach B, Salvi R . Noise-induced hearing loss induces loudness intolerance in a rat Active Sound Avoidance Paradigm (ASAP). Hear Res. 2017; 353:197-203. PMC: 5642041. DOI: 10.1016/j.heares.2017.07.001. View

16.

Iwata H, Uga Y, Yoshioka Y, Ebana K, Hayashi T . Bayesian association mapping of multiple quantitative trait loci and its application to the analysis of genetic variation among Oryza sativa L. germplasms. Theor Appl Genet. 2007; 114(8):1437-49. DOI: 10.1007/s00122-007-0529-x. View

17.

Kis A, Bence M, Lakatos G, Pergel E, Turcsan B, Pluijmakers J . Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris). PLoS One. 2014; 9(1):e83993. PMC: 3893090. DOI: 10.1371/journal.pone.0083993. View

18.

Hydbring-Sandberg E, von Walter L, Hoglund K, Svartberg K, Swenson L, Forkman B . Physiological reactions to fear provocation in dogs. J Endocrinol. 2004; 180(3):439-48. DOI: 10.1677/joe.0.1800439. View

19.

Dodman N, Karlsson E, Moon-Fanelli A, Galdzicka M, Perloski M, Shuster L . A canine chromosome 7 locus confers compulsive disorder susceptibility. Mol Psychiatry. 2009; 15(1):8-10. DOI: 10.1038/mp.2009.111. View

20.

Yoshikawa T, Kikuchi M, Saito K, Watanabe A, Yamada K, Shibuya H . Evidence for association of the myo-inositol monophosphatase 2 (IMPA2) gene with schizophrenia in Japanese samples. Mol Psychiatry. 2001; 6(2):202-10. DOI: 10.1038/sj.mp.4000835. View