title: A unified genetic theory for sporadic and inherited autism.
abstract: Autism is among the most clearly genetically determined of all cognitive-developmental disorders, with males affected more often than females. We have analyzed autism risk in multiplex families from the Autism Genetic Resource Exchange (AGRE) and find strong evidence for dominant transmission to male offspring. By incorporating generally accepted rates of autism and sibling recurrence, we find good fit for a simple genetic model in which most families fall into two types: a small minority for whom the risk of autism in male offspring is near 50%, and the vast majority for whom male offspring have a low risk. We propose an explanation that links these two types of families: sporadic autism in the low-risk families is mainly caused by spontaneous mutation with high penetrance in males and relatively poor penetrance in females; and high-risk families are from those offspring, most often females, who carry a new causative mutation but are unaffected and in turn transmit the mutation in dominant fashion to their offspring.
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Zhao
authors.forename: Anthony
authors.initials: A
authors.lastname: Leotta
authors.forename: Vlad
authors.initials: V
authors.lastname: Kustanovich
authors.forename: Clara
authors.initials: C
authors.lastname: Lajonchere
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: Kiely
authors.initials: K
authors.lastname: Law
authors.forename: Paul
authors.initials: P
authors.lastname: Law
authors.forename: Shanping
authors.initials: S
authors.lastname: Qiu
authors.forename: Catherine
authors.initials: C
authors.lastname: Lord
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sebat
authors.forename: Kenny
authors.initials: K
authors.lastname: Ye
authors.forename: Michael
authors.initials: M
authors.lastname: Wigler
mesh_terms: D001321:Autistic Disorder / Q000145:classification / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D016208:Databases, Factual; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008957:Models, Genetic; D012307:Risk Factors; D012727:Sex Characteristics; D012955:Societies, Medical