| 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-? 3 subunit gene (ITGB3) gene at 17q21.32 has been implicated in psychiatric disorders. We therefore hypothesized thatITGB3gene 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 theITGB3gene with AAO in SCZ in two Caucasian samples (2,166 cases and 2,525 controls) using linear regression analysis and meta-analysis. We observed fourITGB3单核苷酸多态性与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 ofITGB3with AAO. Three disease-associated SNPs were located at species-conserved regions, indicating functional importance. This is the first report which shows thatITGB3variants 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. |