Harnessing new discoveries in infant genetics to deliver innovations in understanding autism

Autism is a highly heritable condition that emerges during infancy and toddlerhood, a fundamental period for brain development in all children. Both recent theory and evidence indicates that infancy is a critical developmental stage for autism. Although a major influence on the cause of autism is common genetic variation, there is a stark lack of information about the common genetic variation that influences general infant development, creating a notable barrier for understanding its contribution in autism.

Over the last three years, Angelica Ronald has led a collaboration to complete large-scale genome-wide association studies of major domains on infant and toddler neurodevelopment. These include social development, motor development, emotional development, activity level and early infant fussiness. These new infant genetic discoveries offer an opportunity to frame our understanding of autism within the broader genetic architecture of infant development, potentially improving mechanistic insight and early identification of autism.

Drawing on these recent GWAS, the project will identify to what degree the genetic architecture of autism overlaps with that of infant and toddler development and the ways in which the genetic architecture of autism has separate biological pathways to general infant and toddler development (the genetics aim).

Second, the project will tackle how inherited common genetic variation influencing infancy and toddler development plays a role in the autism phenotype (the phenotype aim). Polygenic scores will be calculated for infant traits from our new infant GWAS and data will be analysed from the SPARK and Simons Searchlight samples. We will study if inherited common genetic variation underlying infancy and toddler development impacts symptomatology, co-occurring conditions and adaptive functioning in autism. We will test this in autistic individuals with known genetic causes and with unknown etiology.

Third, with data from the developing Human Connectome Project, the project will isolate the brain structures and functional architecture impacted by the genetic variation influencing infant and toddler development and autism (the brain aim). Together, these three aims hope to significantly advance understanding of the early biological basis of autism and its phenotypic presentation.