Journal article
A genome-wide linkage and association scan reveals novel loci for autism
Nature, Vol.461(7265), pp.802-808
10/2009
DOI: 10.1038/nature08490
PMCID: PMC2772655
PMID: 19812673
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.
Details
- Title: Subtitle
- A genome-wide linkage and association scan reveals novel loci for autism
- Creators
- Lauren Weiss - Massachusetts General Hospital [Boston]Dan Arking - Johns Hopkins UniversityMark Daly - University of HelsinkiAravinda Chakravarti - Johns Hopkins UniversityCatalina Betancur - Génétique de l'autisme = Genetics of AutismGene Discovery Project of Johns HopkinsAutism Consortium
- Contributors
- Val C Sheffield (Contributor) - University of Iowa, Stead Family Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- Nature, Vol.461(7265), pp.802-808
- DOI
- 10.1038/nature08490
- PMID
- 19812673
- PMCID
- PMC2772655
- NLM abbreviation
- Nat Cell Biol
- ISSN
- 0028-0836
- eISSN
- 1476-4679
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 10/2009
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984065389602771
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