Document Detail

Transmission disequilibrium testing of the chromosome 15q11-q13 region in autism.
MedLine Citation:
PMID:  18361419     Owner:  NLM     Status:  MEDLINE    
Evidence implicates the serotonin transporter gene (SLC6A4) and the 15q11-q13 genes as candidates for autism as well as restricted repetitive behavior (RRB). We conducted dense transmission disequilibrium mapping of the 15q11-q13 region with 93 single nucleotide polymorphisms (SNPs) in 86 strictly defined autism trios and tested association between SNPs and autism using the transmission disequilibrium test (TDT). As exploratory analyses, parent-of-origin effects were examined using likelihood-ratio tests (LRTs) and genotype-phenotype associations for specific RRB using the Family-Based Association Test (FBAT). Additionally, gene-gene interactions between nominally associated 15q11-q13 variants and 5-HTTLPR, the common length polymorphism of SLC6A4, were examined using conditional logistic regression (CLR). TDT revealed nominally significant transmission disequilibrium between autism and five SNPs, three of which are located within close proximity of the GABA(A) receptor subunit gene clusters. Three SNPs in the SNRPN/UBE3A region had marginal imprinting effects. FBAT for genotype-phenotype relations revealed nominally significant association between two SNPs and one ADI-R subdomain item. However, both TDT and FBAT were not statistically significant after correcting for multiple comparisons. Gene-gene interaction analyses by CLR revealed additive genetic effect models, without interaction terms, fit the data best. Lack of robust association between the 15q11-q13 SNPs and RRB phenotypes may be due to a small sample size and absence of more specific RRB measurement. Further investigation of the 15q11-q13 region with denser genotyping in a larger sample set may be necessary to determine whether this region confers risk to autism, indicated by association, or to specific autism phenotypes.
Soo-Jeong Kim; Camille W Brune; Emily O Kistner; Susan L Christian; Eric H Courchesne; Nancy J Cox; Edwin H Cook
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics     Volume:  147B     ISSN:  1552-485X     ISO Abbreviation:  Am. J. Med. Genet. B Neuropsychiatr. Genet.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-24     Completed Date:  2008-11-17     Revised Date:  2014-09-04    
Medline Journal Info:
Nlm Unique ID:  101235742     Medline TA:  Am J Med Genet B Neuropsychiatr Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1116-25     Citation Subset:  IM    
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MeSH Terms
Autistic Disorder / genetics*
Child, Preschool
Chromosomes, Human, Pair 15 / genetics*
Gene Regulatory Networks
Genetic Predisposition to Disease*
Genomic Imprinting
Linkage Disequilibrium
Polymorphism, Single Nucleotide*
Receptors, GABA-A / genetics
Serotonin Plasma Membrane Transport Proteins / genetics
Grant Support
AS1583//Autism Speaks; U19 HD035482/HD/NICHD NIH HHS; U19 HD35482/HD/NICHD NIH HHS
Reg. No./Substance:
0/Receptors, GABA-A; 0/SLC6A4 protein, human; 0/Serotonin Plasma Membrane Transport Proteins

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