Familial Genomic Architecture in Autism: A Trio-Based Multiscale Extension of the Genomic Complexity Index (GCI)

Abstract

This record presents an exploratory single-family genomic study and methodological proof of concept focused on autism spectrum disorder (ASD). A father–mother–child trio was evaluated through sequential layers of Mendelian quality control, pedigree-aware phasing, reference-panel imputation, functional annotation, current ClinVar assessment, parental-transmission analysis, independent ASD polygenic-score sensitivity analyses, and ancestry-aware population-structure control.The principal contribution is methodological rather than etiological. Directly observed trio data showed very high Mendelian compatibility, while carrier-aware ClinVar filtering did not identify a simple, rare, unambiguous, adequately reviewed Mendelian explanation within the resolution of the available platform. Transmission among directly observed informative parental loci was approximately balanced. Two independent ASD polygenic scores did not replicate directionally. Population-structure analysis, performed exclusively with directly observed, common, LD-pruned SNPs, placed the trio within a European-shifted region of the admixed-American continuum represented by the 1000 Genomes Phase 3 reference panel. The child remained close to the parental midpoint across principal-component space, providing an additional internal consistency check.This study therefore does not establish the genetic etiology of autism in the general population and should not be interpreted as a clinical genetic report. Its value lies in demonstrating how progressively stricter genomic controls can distinguish stable observations from fragile or method-sensitive interpretations. The work also situates the family analysis within a broader multiscale view of autism genetics, in which genomic variation, regulatory context, developmental processes, and neural-network dynamics are considered interacting levels rather than isolated explanatory factors.Raw family genomic files and individual-level genotype tables are not included in this public deposit in order to preserve participant privacy.