Linkage analysis for autism in a subset families with obsessive-compulsive behaviors

Evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19

J. D. Buxbaum, J. Silverman, M. Keddache, C. J. Smith, Eric Hollander, N. Ramoz, J. G. Reichert

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)144-150
Number of pages7
JournalMolecular Psychiatry
Volume9
Issue number2
DOIs
StatePublished - 2004
Externally publishedYes

Fingerprint

Compulsive Behavior
Chromosomes, Human, Pair 19
Obsessive Behavior
Chromosomes, Human, Pair 6
Chromosomes, Human, Pair 1
Autistic Disorder
Genes
Chromosomes, Human, Pair 4
Genome
Interviews

Keywords

  • Autistic disorder
  • OCD
  • Repetitive behaviors

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

Cite this

Linkage analysis for autism in a subset families with obsessive-compulsive behaviors : Evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19. / Buxbaum, J. D.; Silverman, J.; Keddache, M.; Smith, C. J.; Hollander, Eric; Ramoz, N.; Reichert, J. G.

In: Molecular Psychiatry, Vol. 9, No. 2, 2004, p. 144-150.

Research output: Contribution to journalArticle

@article{507a550bda534df6a5c3021f6197eca8,
title = "Linkage analysis for autism in a subset families with obsessive-compulsive behaviors: Evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19",
abstract = "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.",
keywords = "Autistic disorder, OCD, Repetitive behaviors",
author = "Buxbaum, {J. D.} and J. Silverman and M. Keddache and Smith, {C. J.} and Eric Hollander and N. Ramoz and Reichert, {J. G.}",
year = "2004",
doi = "10.1038/sj.mp.4001465",
language = "English (US)",
volume = "9",
pages = "144--150",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "2",

}

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, Eric

AU - Ramoz, N.

AU - Reichert, J. G.

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

UR - http://www.scopus.com/inward/record.url?scp=1542284674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1542284674&partnerID=8YFLogxK

U2 - 10.1038/sj.mp.4001465

DO - 10.1038/sj.mp.4001465

M3 - Article

VL - 9

SP - 144

EP - 150

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 2

ER -