title: Genetic association analysis of ITGB3 polymorphisms with age at onset of schizophrenia.
abstract: Schizophrenia (SCZ) is a debilitating disorder with a prevalence of approximately 1 % worldwide. SCZ is known to have a high degree of genetic and clinical heterogeneity and is a major health problem worldwide. The integrin-β 3 subunit gene (ITGB3) gene at 17q21.32 has been implicated in psychiatric disorders. We therefore hypothesized that ITGB3 gene polymorphisms might also play a role in SCZ and age at onset (AAO) of SCZ. We investigated the genetic associations of 23 single-nucleotide polymorphisms (SNPs) of the ITGB3 gene with AAO in SCZ in two Caucasian samples (2,166 cases and 2,525 controls) using linear regression analysis and meta-analysis. We observed four ITGB3-SNPs associated with AAO in SCZ in a non-Genetic Association Information Network (GAIN) sample (p < 10(-3)). Three of these four SNPs were replicated in the GAIN sample. The SNP rs16941771 was most significantly associated with AAO (p = 7.47 × 10(-5)). Meta-analysis showed that 6 of 23 SNPs were associated with AAO. The haplotype analysis also supports the association of ITGB3 with AAO. Three disease-associated SNPs were located at species-conserved regions, indicating functional importance. This is the first report which shows that ITGB3 variants are associated with AAO in SCZ, providing direct evidence of the use of AAO as an intermediate phenotype to dissect the complex genetics of SCZ.
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, PO Box 70259, Lamb Hall, Johnson City, TN, 37614-1700, USA, wangk@etsu.edu.
authors.forename: Ke-Sheng
authors.initials: KS
authors.lastname: Wang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Liu
authors.forename: Tania Bedard
authors.initials: TB
authors.lastname: Arana
authors.forename: Nicholas
authors.initials: N
authors.lastname: Thompson
authors.forename: Henry
authors.initials: H
authors.lastname: Weisman
authors.forename: Cecilia
authors.initials: C
authors.lastname: Devargas
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Mao
authors.forename: Brenda Bin
authors.initials: BB
authors.lastname: Su
authors.forename: Cynthia
authors.initials: C
authors.lastname: Camarillo
authors.forename: Michael A
authors.initials: MA
authors.lastname: Escamilla
authors.forename: Chun
authors.initials: C
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*
chemical_list: C061248:ITGB3 protein, human; D039661:Integrin beta3