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.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-17850 |
| Date | 01 September 2011 |
| Creators | Wang, Ke Sheng, Liu, Xuefeng, Zhang, Qunyuan, Aragam, Nagesh, Pan, Yue |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
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