2026-10-07T07:04:03Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33339309 2026-10-06T09:53:48Z category_24310 category_24316 category_24187 portal_803 item_type_3 month_year_10_2026

Dog-human gene network colocalization links synaptic signalling and ubiquitination to compulsive disorders Katarina Tengvall (13917495) Vista Sohrab (24716645) Matthew J. Christmas (17353813) Gustaf Brander (18658597) Kathryn A. Lord (11388617) Elinor K. Karlsson (15081105) Jennifer Meadows (9096907) Kerstin Lindblad-Toh (8653836) Genomics Neurogenetics Biological network analysis dog ocd comparative genomics compulsive disorders gene network models <p dir="ltr">Obsessive-compulsive disorder (OCD) is highly polygenic, and the largest genome-wide association study (GWAS) to date — 53,660 cases and 2,044,417 controls — identified only 30 loci, a small fraction of those expected to cause disease and too few to resolve the underlying biological pathways. Some dogs naturally develop a compulsive disorder (dogCD) with parallels to human OCD, and the distinctive population structure of pet dogs reduces sample sizes needed for discovery of associated loci.</p><p dir="ltr">Here, we generated high-density genotypes (SNPs_max= 9,885,182, MAF ≥ 1%) for 2,584 dogs with measures across 14 items and 3 factors describing the dogCD phenotypes using low-pass sequencing (mean depth = 0.83, s.d. = 0.35, N = 2,211) or SNP arrays (Axiom Canine Array A+B with 1,011,992 SNPs, N = 373) followed by imputation with the Dog10K reference panel. We tested for association using mixed-model approaches that account for population structure: MLMA-LOCO for the three latent factors and POLMM for 14 ordinal survey items and combined results to define a consensus set of non-overlapping associated loci.</p><p dir="ltr">We then use cross-species network colocalization to combine the GWAS in 2,584 dogs, recruited through the community science project Darwin's Ark, with the OCD GWAS, identifying a 165-gene network not discernible from the current human data alone. Combining dog and human GWAS implicates an inherited risk architecture largely outside current OCD pharmacotherapy and establishes pet dogs as a tractable model for psychiatric gene network discovery, particularly for conditions underpowered in human studies alone.</p><p dir="ltr">Data in storage includes Darwin's Ark genotype files:</p><ol><li>affy_round3 = Axiom Canine Array A+B with 1,011,992 SNPs, N = 411 mapped to CanFam3.1</li><li>DA_MERGED_GENCOVE_AXIOM_QC5 = 3328 dogs & 12518078 SNPs mapped to CanFam4. Imputed with the Dog10K reference panel. Dataset is merged from Axiom Canine array (lifted and imputed, N=411) and Gencove low-pass sequencing (mapped to Cf4 and imputed, N=2917). This is the dataset before separating them into 17 dogCD phenotypes.</li><li>17 sets of sumstats (ITEM*sumstats & CCDF*_sumstats) from the GWAS of each items (N=14) and factor (N=3).</li><li>ALLFAM_sex_age_phenos.txt includes all phenotypes and covariates for dogs included in each separate plink gwas files (OBS for CCDF1 and CCF2: dogs with factor scores with only one item loading to that factor are excluded).</li><li>DarwinsArk_20220715_dogs_genotyped_breed_sex.csv = Darwin's Ark breed and sex metadata (columns: dog, purebred, breed1_inputted, sex) for the 3,269 genotyped dogs, a subset of the Darwin's Ark dog table (2022-07-15 release). Used for the population-structure PCA plot.</li></ol><p><br></p> 2026-10-06T09:53:48Z Dataset Dataset 10.17044/scilifelab.33339309.v3 https://figshare.com/articles/dataset/Dog-human_gene_network_colocalization_links_synaptic_signalling_and_ubiquitination_to_compulsive_disorders/33339309 CC BY 4.0