Stratification based on language-related endophenotypes in autism: attempt to replicate reported linkage.

Full Abstract

The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism-related susceptibility regions. To further explore the utility of using language-related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage. A whole genome scan using a multipoint non-parametric linkage approach was performed in 133 families, stratifying the sample by phrase speech delay and word delay (WD). None of the regions reached suggested genome-wide or replication significance thresholds. However, several loci on chromosomes 1, 2, 4, 6, 7, 8, 9, 10, 12, 15, and 19 yielded nominally higher linkage signals in the delayed groups. The results did not support reported linkage findings for loci on chromosomes 7 or 13 that were a result of stratification based on the language delay endophenotype. In addition, inclusion of information on parental history of language delay did not appreciably affect the linkage results. The nominal increase in NPL scores across several regions using language delay endophenotypes for stratification suggests that this strategy may be useful in attenuating heterogeneity. However, the inconsistencies in regions identified across studies highlight the importance of increasing sample sizes to provide adequate power to test replications in independent samples.

Learn Faster Today Improve your study skills

Author information

Author/s: Spence, Sarah J (SJ); Cantor, Rita M (RM); Chung, Lien (L); Kim, Sharon (S); Geschwind, Daniel H (DH); Alarcón, Maricela (M);

Affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, California 90095, USA.

Grants: MH-068172 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet), published in United States. (Language: eng)

Reference: 2006-Sep; vol 141B (issue 6) : pp 591-8

Dates: Created 2006/08/30; Completed 2006/10/18; Revised 2008/05/21;

PMID: 16752361, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article (including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Autistic Disorder - genetics
Genotype
Humans

These are the highest related articles currently in the database:

Current directions in research on autism. 30 Dec 2000
The neurobiology of autism: new pieces of the puzzle. 27 Feb 2003
Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13. 29 Jun 2003
Paediatrics: genetic insights and long-term follow-up. 30 Dec 2004
[Autism and metabolic disorders-a rational approach] 29 Sep 2005
[The genetics of autistic disorders] 30 Dec 2007
Value of a clinical morphology examination in autism. 8 Apr 2000
Variable expression of the autism broader phenotype: findings from extended pedigrees. 29 Apr 2000
Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation. 30 May 2000
The search for autism's roots. 19 Jun 2001

See 100+ related articles.