M61. TRANSMISSION DISEQUILIBRIUM TEST ANALYSIS OF COMMON VARIANTS AND THEIR ASSOCIATION WITH AUTISM IN COLOMBIAN FAMILIES

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social communication and behavior. Although genetic studies have historically focused on rare variants due to their significant impact on the autism phenotype, common variants also play an important role in ASD susceptibility. To date, most studies have focused on Caucasian populations, limiting the genetic understanding of this condition in Latin American populations, including the Colombian population. The Transmission Disequilibrium Test (TDT) is a statistical method that detects the overtransmission of alleles from healthy parents to children affected by the condition, reducing population stratification and indicating a possible association with ASD. This study aims to investigate the transmission patterns of common genetic variants in Colombian trio families and contribute to the understanding of the genetic architecture of ASD in admixed populations. SNP microarray genotyping (Illumina Global Screening Array v3.0) from a Colombian cohort of 153 families (affected child, father and/or mother). A quality control pipeline was applied to the raw data using Genome Studio and PLINK 1.9, to eliminate samples and variants of low quality, monomorphic variants, and Mendelian errors. Subsequently, variant imputation was performed, and analysis focused on common biallelic variants (MAF > 0.05). These variants were then subjected to the Transmission Disequilibrium Test (TDT), and the Bonferroni correction was applied to obtain statistically significant common variants with overtransmission from parents to affected offspring. Variant annotation was performed using the Variant Effect Predictor (VEP) tool and public databases such as dbSNP, ClinVar, and gnomAD. The genomic microarray dataset was analyzed using TDT to identify biases in the Mendelian inheritance pattern in Colombian families with a child affected by ASD. The analysis included three approaches: common variants in the Caucasian population previously reported in the scientific literature as associated with ASD, variants present in genes classified as high-risk by the Autism Sequencing Consortium (ASC), and common variants observed exclusively in this cohort, which have not been previously associated with ASD in other populations. This study proposes a methodological approach to investigate the contribution of common variants in the genetics of ASD in an underrepresented population in genomics studies such as the Colombian population. The identification of variants with biased transmission is considered to have relevant clinical value, especially if they relate to previously reported genes or if they represent new findings in this population. Furthermore, the results contribute to understanding the genetic architecture of ASD in admixed populations and provide a basis for future studies on genetic diagnosis in Latin American contexts.