The enrichment of self-domestication and neural crest function loci in the heritability of neurodevelopmental disorders is not independent of genomic regulatory functions

Abstract

Self-domestication could play an important role in contributing to shape the biology of human brain and the predisposition to neurodevelopmental disorders. Leveraging genome-wide data from the Psychiatric Genomics Consortium, we tested the enrichment of self-domestication and neural crest function loci with respect to the heritability of autism spectrum disorder, schizophrenia (SCZ in East Asian and European ancestries, EAS and EUR, respectively), attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and Tourettes syndrome (TS). Considering only self-domestication and neural-crest-function annotations in the linkage disequilibrium score regression (LDSC) model, our partitioned heritability analysis revealed statistically significant enrichments across all disorders investigated. The estimates of the heritability enrichments for self-domestication loci were similar across neurodevelopmental disorders, ranging from 0.902 (EAS SCZ, p=4.55x10-20) to 1.577 (TS, p=5.85x10-5). Conversely, a wider spectrum of heritability enrichment estimates was present for neural crest function with the highest enrichment observed for TS (enrichment=3.453, p=2.88x10-3) and the lowest for EAS SCZ (enrichment=1.971, p=3.8lx10-3). Although these estimates appear to be strong, the enrichments for self-domestication and neural crest function were null once we included additional annotations related to different genomic features. This indicates that the effect of self-domestication on the polygenic architecture of neurodevelopmental disorders is not independent of other functions of human genome.