Identification of moderate effect size genes in autism spectrum disorder through a novel gene pairing approach
Caballero, M.; Satterstrom, F. K.; Buxbaum, J.; Mahjani, B.
Show abstract
Autism Spectrum Disorder (ASD) arises from complex genetic and environmental factors, with inherited genetic variation playing a substantial role. This study introduces a novel approach to uncover moderate effect size (MES) genes in ASD, which individually do not meet the ASD liability threshold but collectively contribute when paired with specific other MES genes. Analyzing 10,795 families from the SPARK dataset, we identified 97 MES genes forming 50 significant gene pairs, demonstrating a substantial association with ASD when considered in tandem, but not individually. Our method leverages familial inheritance patterns and statistical analyses, refined by comparisons against control cohorts, to elucidate these gene pairs contribution to ASD liability. Furthermore, expression profile analyses of these genes in brain tissues underscore their relevance to ASD pathology. This study underscores the complexity of ASDs genetic landscape, suggesting that gene combinations, beyond high impact single-gene mutations, significantly contribute to the disorders etiology and heterogeneity. Our findings pave the way for new avenues in understanding ASDs genetic underpinnings and developing targeted therapeutic strategies.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Association between genes regulating neural pathways for quantitative traits of speech and language disorders 95%
- Exome sequencing of 457 autism families recruited online provides evidence for novel ASD genes 95%
- Neurodevelopmental disorders and cancer networks share pathways; but differ in mechanisms, signaling strength, and outcome 92%
Similar papers in this journal
- A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex 98%
- Decomposition of phenotypic heterogeneity in autism reveals distinct and coherent genetic programs 97%
- Identification of shared and differentiating genetic risk for autism spectrum disorder, attention deficit hyperactivity disorder and case subgroups 97%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.