{
  "abstract": "Obsessive-compulsive disorder (OCD) is highly polygenic, and the largest genome-wide association study (GWAS), with 53,660 cases and 2,044,417 controls, identified only 30 loci, a small fraction of loci estimated to explain its heritability - too few to resolve biological pathways. Pet dogs develop a compulsive disorder (dogCD) similar to OCD. In a GWAS of dogCD with 2,584 dogs from the community science project Darwin's Ark, each dog locus explains at least 40-fold more phenotypic variance than each human OCD locus, giving power equivalent to the human GWAS with 80-fold fewer individuals. Combining the two GWAS identifies a 165-gene network undetectable in humans at current sample sizes. This network is enriched for genes expressed in neurons, particularly in the amygdala and cortex, and comprises four biological processes: excitatory-inhibitory synaptic transmission, axon guidance and neuron recognition, protein ubiquitination, and adenylyl cyclase-activating G-protein-coupled receptor signaling. Like most complex human traits, dogCD risk is likely driven by regulatory variation: fine-mapped dogCD SNPs are non-coding, and dogCD loci are enriched in candidate cis-regulatory elements (cCREs) in a new dog epigenomic atlas spanning eight brain regions. The cross-species network implicates an inherited risk architecture largely outside current OCD pharmacotherapy, and establishes pet dogs as a model for gene network discovery, particularly for conditions underpowered in human studies.",
  "abstract_shown": true,
  "affiliations": [
    "Uppsala University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "K. Tengvall"
    },
    {
      "name": "V. Sohrab"
    },
    {
      "name": "M. J. Christmas"
    },
    {
      "name": "G. Brander"
    },
    {
      "name": "E. Pederson"
    },
    {
      "name": "R. Pensch"
    },
    {
      "name": "B. Kenney"
    },
    {
      "name": "C. Song"
    },
    {
      "name": "O. Wallerman"
    },
    {
      "name": "E. Sundstrom"
    },
    {
      "name": "C. Wang"
    },
    {
      "name": "A. Karlsson"
    },
    {
      "name": "L. L. Monsen"
    },
    {
      "name": "Nordic OCD and Related Disorders Consortium (NORDiC)"
    },
    {
      "name": "PGC TS/OCD working group"
    },
    {
      "name": "K. A. Lord"
    },
    {
      "name": "N. I. Strom"
    },
    {
      "name": "C. Ruck"
    },
    {
      "name": "D. Mataix-Cols"
    },
    {
      "name": "M. Mattheisen"
    },
    {
      "name": "J. J. Crowley"
    },
    {
      "name": "J. R. S. Meadows"
    },
    {
      "name": "E. Karlsson"
    },
    {
      "name": "K. Lindblad-Toh"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/afkzq0p7p5s7n.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.12.758413",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758413v1.full",
  "id": "afkzq0p7p5s7n",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758413v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genetics"
    ],
    [
      "openalex",
      "3203|Obsessive-Compulsive Spectrum Disorders"
    ]
  ],
  "openalex": "W7213052219",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758413v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/afkzq0p7p5s7n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:22Z",
      "native_id": "10.64898/2026.10.12.758413",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758413v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genetics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Dog-human gene network colocalization links synaptic signalling and ubiquitination to compulsive disorders",
  "title_text": "Dog-human gene network colocalization links synaptic signalling and ubiquitination to compulsive disorders",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:22Z",
  "url": "https://research.draconitic.com/paper/afkzq0p7p5s7n",
  "venue": "bioRxiv",
  "versions": []
}