title: ITGB3 shows genetic and expression interaction with SLC6A4.
abstract: Autism affects more males than females and is associated with disturbances of the serotonin system. The integrin beta3 (ITGB3) and serotonin transporter (SLC6A4) genes were both recently identified as male quantitative trait loci (QTLs) for serotonin levels and alleles of each have been associated with autism. Here, we use publicly available genomic resources to determine whether regulation of expression level could be the mechanism behind association between serotonin level and noncoding variation in ITGB3. We also examine whether ITGB3 might interact with SLC6A4 to contribute to autism susceptibility. Using murine and human expression data, we observe that ITGB3 and SLC6A4 expression levels are correlated (0.38<r<0.78). Moreover, genetic variation in ITGB3 is associated with expression of both ITGB3 (P=0.012) and SLC6A4 (P=0.008) in unrelated CEPH individuals. We also show preliminary evidence that genotypes at the ITGB3 and SLC6A4 loci may interact to affect autism susceptibility (P=0.033).
authors.affiliation: Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA. laweiss@chgr.mgh.harvard.edu
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Weiss
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: C061248:ITGB3 protein, human; D039661:Integrin beta3; D012333:RNA, Messenger; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse