A genome-wide linkage and association scan reveals novel loci for autism.
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Weiss, LA; Arking, DE; Gene Discovery Project of Johns Hopkins & the Autism Consortium, ; Daly, MJ; Chakravarti, A
Published Date
- October 8, 2009
Published In
Volume / Issue
- 461 / 7265
Start / End Page
- 802 - 808
PubMed ID
- 19812673
Pubmed Central ID
- 19812673
Electronic International Standard Serial Number (EISSN)
- 1476-4687
Digital Object Identifier (DOI)
- 10.1038/nature08490
Language
- eng
Conference Location
- England