# The genetic architecture of neurodevelopmental disorders

## TL;DR

This paper explores how the genetic causes of rare and common neurodevelopmental disorders may not be as distinct as previously thought.

## Contribution

The paper proposes that the genetic architecture of neurodevelopmental disorders exists on a continuum rather than being strictly divided into monogenic and complex categories.

## Key findings

- Common neurodevelopmental disorders like autism and schizophrenia may have complex genetics due to hidden genetic heterogeneity.
- Even rare, Mendelian disorders often show variability in clinical outcomes influenced by additional genetic factors.
- The distinction between monogenic and complex disorders may be artificial and overlapping.

## Abstract

Neurodevelopmental disorders include rare conditions caused by identified single mutations, such as Fragile X, Down and Angelman syndromes, and much more common clinical categories such as autism, epilepsy and schizophrenia. These common conditions are all highly heritable but their genetics is considered to be “complex”. In fact, this sharp dichotomy in genetic architecture between rare and common disorders may be largely artificial. On the one hand, much of the apparent complexity in the genetics of common disorders may derive from underlying genetic heterogeneity, which has remained obscure until recently. On the other hand, even for supposedly Mendelian conditions, the relationship between single mutations and clinical phenotypes is rarely simple. The categories of monogenic and complex disorders may therefore merge across a continuum, with some mutations being strongly associated with specific syndromes and others having a more variable outcome, modified by the presence of additional genetic variants.