Publication Date:
2009-10-09
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772655/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772655/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weiss, Lauren A -- Arking, Dan E -- Gene Discovery Project of Johns Hopkins & the Autism Consortium -- Daly, Mark J -- Chakravarti, Aravinda -- 1K23MH080954/MH/NIMH NIH HHS/ -- 1R01 MH083565/MH/NIMH NIH HHS/ -- AS2042/Autism Speaks/ -- G0601030/Medical Research Council/United Kingdom -- HD055782/HD/NICHD NIH HHS/ -- MH00219/MH/NIMH NIH HHS/ -- MH00980/MH/NIMH NIH HHS/ -- MH081754/MH/NIMH NIH HHS/ -- MH39437/MH/NIMH NIH HHS/ -- MH52708/MH/NIMH NIH HHS/ -- MH55135/MH/NIMH NIH HHS/ -- MH55284/MH/NIMH NIH HHS/ -- MH60007/MH/NIMH NIH HHS/ -- MH61009/MH/NIMH NIH HHS/ -- MH64547/MH/NIMH NIH HHS/ -- NS042165/NS/NINDS NIH HHS/ -- P50 HD055748/HD/NICHD NIH HHS/ -- P50 HD055782/HD/NICHD NIH HHS/ -- R01 MH060007/MH/NIMH NIH HHS/ -- R01 MH060007-04A1/MH/NIMH NIH HHS/ -- R01 MH060007-05/MH/NIMH NIH HHS/ -- R01 MH060007-06/MH/NIMH NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2009 Oct 8;461(7265):802-8. doi: 10.1038/nature08490.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19812673" target="_blank"〉PubMed〈/a〉
Keywords:
Autistic Disorder/*genetics/metabolism
;
Brain/metabolism
;
Chromosome Mapping
;
Chromosomes, Human, Pair 5/genetics
;
Genetic Linkage/genetics
;
Genetic Predisposition to Disease/*genetics
;
*Genome-Wide Association Study
;
Humans
;
Internationality
;
Membrane Proteins/*genetics/metabolism
;
Nerve Tissue Proteins/*genetics/metabolism
;
Polymorphism, Single Nucleotide/genetics
;
Sample Size
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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