Prematurity and Genetic Liability for Autism Spectrum Disorder

Area of Science:

• Neuroscience
• Genetics
• Pediatrics

Background:

• Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with significant genetic influence.
• Environmental factors like preterm birth are associated with increased ASD risk, but their interaction with genetic predisposition is not fully understood.

Purpose of the Study:

• To investigate the combined impact of genetic liability and preterm birth on Autism Spectrum Disorder (ASD).
• To explore how genetic factors and preterm birth influence ASD presentation and risk.

Main Methods:

• Analysis of phenotype and genetic data from large ASD cohorts (SPARK, SSC) including genome and exome sequencing.
• Utilized generalized estimating equations (GEE) models to assess rare variant burden and polygenic risk scores (PRS).
• Developed a machine learning model to predict ASD in preterm infants using birth-time data.

Main Results:

• Preterm birth exacerbates ASD phenotypic severity, unrelated to ASD genetic factors.
• Preterm infants with ASD showed a higher rate of de novo variants compared to non-ASD preterm infants.
• Higher ASD PRS, preterm birth, and male sex significantly increased ASD probability, approaching 90%.

Conclusions:

• Preterm birth may worsen ASD multimorbidity, but genetic factors increase ASD likelihood in preterm infants.
• Polygenic load for ASD interacts additively with preterm birth, particularly in males.
• Integrating genetic assessments into neonatal care could improve early ASD identification and intervention for preterm infants.