Uncovering the genes that contribute to the variability in brain regions involved in language processing might shed light on the evolution of brain structures essential to the emergence of language in Homo sapiens. The superior temporal asymmetrical pit (STAP), which is not observed in chimpanzees, represents an ideal phenotype to investigate the genetic variations that support human communication. The depth of the left STAP was significantly associated with a DACT1 enhancer region in the UK Biobank British discovery sample (N=16,515). This association was replicated in the IMAGEN cohort (N=1,726) and the UK Biobank non-British validation sample (N=2,161). This genomic region was also associated to a lesser extent with the right STAP depth and the formation of sulcal interruptions, plis de passage, in the bilateral STAP but not with other structural brain MRI phenotypes, highlighting its specific expression in the superior temporal regions. Diffusion MRI emphasized an association with the fractional anisotropy of the left auditory fibers of the corpus callosum and with networks involved in linguistic processing in resting-state functional MRI. Finally, DACT1 is mainly expressed during the first two trimesters of pregnancy just before the superior temporal sulcus becomes visible and the first evidence of speech processing is observed in preterm neonates. Overall, this evidence demonstrates a significant, specific relationship between variants in this genomic region and the establishment of the superior temporal regions that support human communication.
Significance statementThe search for "language genes" has mainly focused on families with language disorders. Here, using a macroscopic marker of cerebral asymmetry observed only in humans, the STAP, we discovered a genetic variant that modulates many anatomical and functional features of the superior temporal sulcus, particularly in the left hemisphere, in the general population. Whole-brain analyses showed that this modulation is nearly limited to the superior temporal region. Finally, the gene effect is most significant during the first six months of gestation, decreasing just before the appearance of thalamocortical connectivity that enables external auditory inputs. Thus, we uncovered a genomic region that probably contributes to building the networks underlying human language.