TY - JOUR
T1 - Evidence for a language quantitative trait locus on chromosome 7q in multiplex autism families
AU - Autism Genetic Resource Exchange Consortium
AU - Alarcón, Maricela
AU - Cantor, Rita M.
AU - Liu, Jianjun
AU - Gilliam, T. Conrad
AU - Geschwind, Daniel H.
AU - Bucan, Maja
AU - Brown, W. Ted
AU - Buxbaum, Joseph D.
AU - Greenberg, David A.
AU - Ledbetter, David H.
AU - Miller, Bruce L.
AU - Nelson, Stanley F.
AU - Pevsner, Jonathan
AU - Rotter, Jerome I.
AU - Schellenberg, Gerard D.
AU - Samango-Sprouse, Carole
AU - Tanzi, Rudolph E.
AU - Wilhelmsen, Kirk C.
N1 - Funding Information:
We gratefully acknowledge the contributions of the AGRE families who participated in this study and have made the resource possible. Many thanks to Ms. Nancy Hart for her assistance in accessing the AGRE database and to two anonymous reviewers for their useful suggestions on the manuscript. This project was supported by a postdoctoral research award from the M.I.N.D. Institute, University of California, Davis (to M.A.) and by a Young Investigator Award from the Cure Autism Now (CAN) foundation (to J.L.). AGRE was made possible by funds from the CAN foundation. T.C.G. and J.L. also acknowledge support from the generous contribution of Dr. Judith P. Sulzberger.
PY - 2002/1/1
Y1 - 2002/1/1
N2 - 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; x2 = 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.
AB - 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; x2 = 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.
UR - http://www.scopus.com/inward/record.url?scp=0036138102&partnerID=8YFLogxK
U2 - 10.1086/338241
DO - 10.1086/338241
M3 - Article
C2 - 11741194
AN - SCOPUS:0036138102
SN - 0002-9297
VL - 70
SP - 60
EP - 71
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -