Medicina (B Aires). 2025 Mar;85 Suppl 1:22-29.
ABSTRACT
Neurodevelopmental disorders (NDD) share two main characteristics: their high comorbidity between them and other processes – psychiatric disorders and epilepsy – and their high heritability, with a gap between that extracted through family studies (familial heritability, 0.66) and that obtained through genetic studies (genetic heritability, 0.19). There is a strong genetic correlation between NDD and different behavioral disorders, with a familial genetic correlation coefficient estimated at 0.62, suggesting a shared genetic load that encompasses these processes as well as others such as bipolar disorder, schizophrenia or depression. Missing heritability, mutational load and genetic vulnerability are important concepts for understanding the complex interactions between different NDD and their comorbidities, as well as for illustrating the discrepancy between genetic and familial heritability figures. Genetic vulnerability determines which genes are more likely to cause diseases when mutated; Mutational load accumulates the genetic effects that influence the phenotypic expression of a disorder, and the interaction between different variants (epistasis) and their accumulation, including common variants, can amplify the probability of developing a disorder. Missing heritability illustrates the proportion of heritability not explained by identified genetic variants. Although genome-wide association studies (GWAS) identify common variants associated with diseases, these usually explain only a small part of the total genetic risk. This gap can be related to different factors, including rare variants present in non-coding regions, epigenetic factors that regulate vulnerable genes, and complex interactions between genes.
PMID:40020089
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