TY - JOUR
T1 - Linkage analysis for autism in a subset families with obsessive-compulsive behaviors
T2 - Evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19
AU - Buxbaum, J. D.
AU - Silverman, J.
AU - Keddache, M.
AU - Smith, C. J.
AU - Hollander, E.
AU - Ramoz, N.
AU - Reichert, J. G.
N1 - Funding Information:
This work was supported by the Seaver Autism Research Center and Cure Autism Now, as well as by the National Institute of Mental Health through a STAART grant (U54 MH 066673). We thank AGRE and Dr T Conrad Gilliam for the genotyping data, all of which were performed in the laboratory of Dr Gilliam and can be found on the AGRE website (www.agre.org).
PY - 2004
Y1 - 2004
N2 - Although there is considerable evidence for a strong genetic component to idiopathic autism, several genome-wide screens for susceptibility genes have been carried out with limited concordance of linked loci, reflecting numerous genes of weak effect and/or sample heterogeneity. In the current study, linkage analysis was carried out in a sample of 62 autism-affected relative pairs with more severe obsessive-compulsive behaviors, selected from a larger (n = 115) set of autism-affected relative pairs as a means of reducing sample heterogeneity. Obsessive-compulsive behaviors were assessed using the Autism Diagnostic Interview-Revised (ADI-R). In the sample with more severe obsessive-compulsive behaviors, multipoint NPL scores above 2 were observed on chromosomes 1, 4, 5, 6, 10, 11 and 19, with the strongest evidence for linkage on chromosome 1 at the marker D1S1656, where the multipoint NPL score was 3.06, and the two-point NPL score was 3.21. In follow-up analyses, analyzing the subset of families (n = 35) where the patients had the most severe obsessive-compulsive behaviors generated a multipoint NPL score of 2.76, and a two-point NPL score of 2.79, indicating that the bulk of evidence for linkage was derived from the families most severely affected with obsessive-compulsive behaviors. The data suggest that there is an autism susceptibility gene on chromosome 1 and provide further support for the presence of autism susceptibility genes on chromosomes 6 and 19.
AB - Although there is considerable evidence for a strong genetic component to idiopathic autism, several genome-wide screens for susceptibility genes have been carried out with limited concordance of linked loci, reflecting numerous genes of weak effect and/or sample heterogeneity. In the current study, linkage analysis was carried out in a sample of 62 autism-affected relative pairs with more severe obsessive-compulsive behaviors, selected from a larger (n = 115) set of autism-affected relative pairs as a means of reducing sample heterogeneity. Obsessive-compulsive behaviors were assessed using the Autism Diagnostic Interview-Revised (ADI-R). In the sample with more severe obsessive-compulsive behaviors, multipoint NPL scores above 2 were observed on chromosomes 1, 4, 5, 6, 10, 11 and 19, with the strongest evidence for linkage on chromosome 1 at the marker D1S1656, where the multipoint NPL score was 3.06, and the two-point NPL score was 3.21. In follow-up analyses, analyzing the subset of families (n = 35) where the patients had the most severe obsessive-compulsive behaviors generated a multipoint NPL score of 2.76, and a two-point NPL score of 2.79, indicating that the bulk of evidence for linkage was derived from the families most severely affected with obsessive-compulsive behaviors. The data suggest that there is an autism susceptibility gene on chromosome 1 and provide further support for the presence of autism susceptibility genes on chromosomes 6 and 19.
KW - Autistic disorder
KW - OCD
KW - Repetitive behaviors
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U2 - 10.1038/sj.mp.4001465
DO - 10.1038/sj.mp.4001465
M3 - Article
C2 - 14699429
AN - SCOPUS:1542284674
SN - 1359-4184
VL - 9
SP - 144
EP - 150
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 2
ER -
