title: Evidence for a language quantitative trait locus on chromosome 7q in multiplex autism families.
abstract: Autism is a syndrome characterized by deficits in language and social skills and by repetitive behaviors. We hypothesized that potential quantitative trait loci (QTLs) related to component autism endophenotypes might underlie putative or significant regions of autism linkage. We performed nonparametric multipoint linkage analyses, in 152 families from the Autism Genetic Resource Exchange, focusing on three traits derived from the Autism Diagnostic Interview: "age at first word," "age at first phrase," and a composite measure of "repetitive and stereotyped behavior." Families were genotyped for 335 markers, and multipoint sib pair linkage analyses were conducted. Using nonparametric multipoint linkage analysis, we found the strongest QTL evidence for age at first word on chromosome 7q (nonparametric test statistic [Z] 2.98; P=.001), and subsequent linkage analyses of additional markers and association analyses in the same region supported the initial result (Z=2.85, P=.002; chi(2)=18.84, df 8, P=.016). Moreover, the peak fine-mapping result for repetitive behavior (Z=2.48; P=.007) localized to a region overlapping this language QTL. The putative autism-susceptibility locus on chromosome 7 may be the result of separate QTLs for the language and repetitive or stereotyped behavior deficits that are associated with the disorder.
authors.affiliation: Center for Neurobehavioral Genetics and Neuropsychiatric Research Institute, and Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Maricela
authors.initials: M
authors.lastname: Alarcón
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: T Conrad
authors.initials: TC
authors.lastname: Gilliam
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
mesh_terms: D001321:Autistic Disorder / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D006801:Humans; D007805:Language Development Disorders / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008126:Lod Score; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D009679:Nuclear Family; D019655:Quantitative Trait, Heritable; D012984:Software; D018709:Statistics, Nonparametric