Major contribution of dominant inheritance to autism spectrum disorders (ASDs) in population-based families.
Results of twin studies have shown that autism spectrum disorders (ASDs) are attributable to complex multigenic interactions rather than to a single susceptibility gene. However, the growing number of distinct, individually rare genetic causes of ASDs, mostly copy number variations (CNVs), favors an alternative to the polygenic hypothesis, the two-component model, which suggests that ASDs are caused either by de novo mutation or by dominant inheritance from asymptomatic carriers of such a mutation. To verify this hypothesis, we estimated the distribution of ASD-risk among both catchment area-based families and multiplex families. Our results suggest that the models with more than three risk components are preferable to the two-component model. Our results also suggest that the largest proportion of ASD cases is caused by dominant inheritance. We additionally show that Supplementary information regarding prevalence has a crucial role in analyzing proband-ascertained data.
Nishiyama
Takeshi
T
Clinical Trial Management Center, Nagoya City University Hospital, Nagoya, Japan. nishiyama@minos.ocn.ne.jp
Notohara
Morihiro
M
Sumi
Satoshi
S
Takami
Satoshi
S
Kishino
Hirohisa
H
D000465:Algorithms; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008957:Models, Genetic; D012307:Risk Factors; D035781:Siblings