A genome-wide linkage and association scan reveals novel loci for autism.

Full Abstract

Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.

Author information

Author/s: Weiss, Lauren A (LA); Arking, Dan E (DE); Gene Discovery Project of Johns Hopkins & the Autism Consortium; Daly, Mark J (MJ); Chakravarti, Aravinda (A);

Affiliation: Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.

Grants: 1K23MH080954 (Agency:NIMH NIH HHS) ; 1R01 MH083565 (Agency:NIMH NIH HHS) ; HD055782 (Agency:NICHD NIH HHS) ; MH00219 (Agency:NIMH NIH HHS) ; MH00980 (Agency:NIMH NIH HHS) ; MH081754 (Agency:NIMH NIH HHS) ; MH39437 (Agency:NIMH NIH HHS) ; MH52708 (Agency:NIMH NIH HHS) ; MH55135 (Agency:NIMH NIH HHS) ; MH55284 (Agency:NIMH NIH HHS) ; MH60007 (Agency:NIMH NIH HHS) ; MH61009 (Agency:NIMH NIH HHS) ; MH64547 (Agency:NIMH NIH HHS) ; NS042165 (Agency:NINDS NIH HHS) ; U54 RR020278 (Agency:NCRR NIH HHS) ; (Agency:Medical Research Council)

Journal and publication information

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

Journal: Nature (Nature), published in England. (Language: eng)

Reference: 2009-Oct; vol 461 (issue 7265) : pp 802-8

Dates: Created 2009/10/08; Completed 2009/10/20; Revised 2009/11/05;

PMID: 19812673, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )

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.