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

Published

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 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

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature08490

Language

  • eng