A quantitative trait locus analysis of social responsiveness in multiplex autism families.
OBJECTIVE
Autism is a complex genetic disorder with a highly heterogeneous phenotype defined by repetitive behaviors, language deficits, and problems with reciprocal social interactions. The authors present the first genome-wide scan for a social endophenotype in autism using the Social Responsiveness Scale, which provides a quantitative measure of autistic-like behavior, primarily focused on social relatedness.


METHODS
A nonparametric quantitative genome scan was performed using the Social Responsiveness Scale in a cohort of about 100 families with two or more autistic probands from the Autism Genetic Resource Exchange to identify autism loci. To determine which additional loci were detected, linkage analysis with the same autism cohort using the qualitative diagnosis of autism was performed. To assess whether there were likely to be sex-specific genetic risk factors, the cohort was stratified by the sex of affected individuals.


RESULTS
The quantitative Social Responsiveness Scale genome scan identified two loci on chromosomes 11 and 17, with the highest score on chromosome 11 (z=3.22). In contrast, no linkage signals reached significance in the Autism Diagnostic Interview-Revised qualitative scan. The Social Responsiveness Scale scan with only male affected identified the same signals on chromosomes 11 and 17, as well as three other regions on chromosomes 4, 8, and 10.


CONCLUSIONS
This study demonstrates the utility of the Social Responsiveness Scale quantitative endophenotype to detect autism-related genetic loci using quantitative behavioral information that may more closely relate to underlying genetic factors.
Duvall
Jacqueline A
JA
Department of Neurology, University of California, Los Angeles, USA.
Lu
Ake
A
Cantor
Rita M
RM
Todd
Richard D
RD
Constantino
John N
JN
Geschwind
Daniel H
DH
D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D002648:Child; D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D015331:Cohort Studies; D005190:Family; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D010641:Phenotype; D012307:Risk Factors; D012919:Social Behavior