Autism Heterogeneity Related to Preterm Birth: Multi-Ancestry Results From the Simons Foundation Powering Autism...

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Perinatal Health

Background:

• Autism spectrum disorder (ASD) exhibits significant clinical variability.
• Preterm birth is a known risk factor for ASD, affecting approximately 13% of individuals.
• The interplay between genetic variation, preterm birth, and ASD heterogeneity is not well understood.

Purpose of the Study:

• To investigate genetic factors associated with preterm birth in individuals with ASD.
• To explore the relationship between genetic variation, preterm birth, and ASD heterogeneity across different ancestries.
• To assess the contribution of common genetic variants to preterm birth in ASD.

Main Methods:

• Genome-wide association studies (GWAS) were conducted across three ancestry groups (African/African American, admixed American, non-Finnish European) within the SPARK cohort.
• A meta-analysis of preterm birth cases and controls was performed using METAL.
• Functional mapping, gene-based analyses, and polygenic risk score (PRS) computations were utilized.

Main Results:

• Ancestry-specific genetic loci associated with preterm birth were identified in ASD cases.
• An estimated 14% single nucleotide polymorphism heritability indicated a contribution from common genetic variants.
• Polygenic liability to preterm birth in the general population was associated with certain congenital anomalies.

Conclusions:

• Findings underscore the importance of considering diverse ancestries and early-life exposures in ASD heterogeneity.
• Future research should focus on larger sample sizes and the role of rare variants in preterm birth and ASD.
• Further investigation is needed to clarify the link between gestational duration and clinical/genetic differences in ASD.