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Genome scans of diverse dog behaviors implicate a neurodevelopmental gene network in mammalian adaptation and psychopathology

Genetic studies show a general factor associated with all human personality and psychopathology, but its basis is unknown. We performed genome scans of 17 normal and problem behaviors in three multi- breed dog cohorts. 21 of 90 mapped loci were supported for the same, or a related, trait in a second cohort. Several of those loci were also associated with brain structure differences across breeds; and five of the respective top-candidate genes are also associated with human brain structure and function. More broadly, the geneset of canine behavioral scans is supported by enrichment for genes mapped for human behavior, personality, psychopathology and brain structure. The biology implicated includes, neurogenesis, axon guidance, angiogenesis, brain structure, alternative splicing, disease association, Hox-family transcription factors, and subiculum expression. Because dog behavior is correlated with body size, we isolated the effect of body size/height in the dog mapping and in the comparative human UK Biobank analyses. Our dog and human findings are consistent with pleiotropy of diverse brain traits with energy metabolism, height, longevity and reproduction. We propose a genetic network underlies neuron birth and development across the life course, and is associated with evolutionary adaptation of behavior and the general psychopathology factor. This understanding has implications for all common psychiatric disorders, and suggests how their risk could be impacted by environmental effects on the IGF1/growth factor signaling-PI3K-AKT-mTOR axis.