Autism spectrum disorder (ASD) has a complex inheritance pattern and is more common in males. Etiological models suggest that majority of ASD risk is transmitted through common and rare de-novo genetic variation. It has been hypothesized that rare variation could be inherited and therefore contribute to the overall risk-burden in subsequent generations, especially through female lineage in disorders with male-skewed sex-ratios. Here we test this hypothesis using multigeneration information on paternal age, because burden of de-novo mutations has been linked to paternal age, and there is a well-established association between older age of fathers and ASD.
Radically different