Using rare genetic mutations to revisit structural brain asymmetry

Abstract

Asymmetry between the left and right brain is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variant studies, which typically exert small effects on brain phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We quantitatively dissected the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior mapping highlights the consequences of genetically controlled brain lateralization on human-defining cognitive traits.

High-effect gene-coding variants impact cognition, mental well-being, and neighborhood safety substrates in brain morphology

“…Specifically, both classes of CNVs were linked to adverse impacts on family well-being, as seen in the adverse effects on cognitive functioning, mental health, and socioeconomic outcomes. Our results also highlight the similar ramifications for cognition and behavior associated with deletions and duplication despite their distinct effects on brain anatomy, corroborating some of our earlier CNV-imaging studies on the UK Biobank 8,27 . Finally, we demonstrated that different genomic characteristics drive these shifts in behavior differentiation and brain maturation.…”