Genome-Wide Association Analysis of Age at Onset in Schizophrenia in a European-American Sample
Document Type
Article
Publication Date
9-1-2011
Description
We performed a genome-wide association analysis to identify genetic variants influencing age at onset (AAO) and examine gene×gender interactions for AAO in schizophrenia (SCZ) using a European-American sample (1,162 cases). Linear regression model in PLINK was used to test for associations with AAO while the GxE option was chosen to test for the influence of gene×gender interactions. The most significant association with AAO was observed with SNP rs7819815 (P=3.10×10-7) at 8q24.22. The next best signal was at 4q25 in COL25A1 gene (rs17039583, P=4.30×10-6) and the third region was at 4p16.1 (rs17407555, P=4.56×10-6, near RAF1P1, and rs4697924, P=1.23×10-5 within WDR1 gene). Conditional analysis on chromosome 4 indicated that 4p16.1 and 4q25 loci were independent. Furthermore, 2 SNPs (rs16834822 and rs16834824) at 1q43 in RYR2 showed strong associations in the female sample (P=2.10×10-6 and 2.33×10-6, respectively) and strong gene×gender interactions in influencing AAO (P=9.23×10-7 and 1.15×10-6, respectively) while the second best region showing gene×gender interaction was at 7q22.3 (rs179863, P=2.33×10-6). Using an independent sample of 1,068 cases, we could not replicate the associations for above top SNPs; however, we found nominal significance associations for their flanking SNPs (P<0.05). These findings provide evidence of several genetic variants influencing AAO of SCZ.
Citation Information
Wang, Ke Sheng; Liu, Xuefeng; Zhang, Qunyuan; Aragam, Nagesh; and Pan, Yue. 2011. Genome-Wide Association Analysis of Age at Onset in Schizophrenia in a European-American Sample. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. Vol.156(6). 671-680. https://doi.org/10.1002/ajmg.b.31209 PMID: 21688384 ISSN: 1552-4841