| 1 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2011 Sep 156B: 671-80 |
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| PMID | 21688384 |
| Title | Genome-wide association analysis of age at onset in schizophrenia in a European-American sample. |
| Abstract | 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. |
| SCZ Keywords | schizophrenia |
| 2 | Eur. J. Hum. Genet. 2016 Jun 24: 944-8 |
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| PMID | 26508570 |
| Title | De novo variants in sporadic cases of childhood onset schizophrenia. |
| Abstract | Childhood-onset schizophrenia (COS), defined by the onset of illness before age 13 years, is a rare severe neurodevelopmental disorder of unknown etiology. Recently, sequencing studies have identified rare, potentially causative de novo variants in sporadic cases of adult-onset schizophrenia and autism. In this study, we performed exome sequencing of 17 COS trios in order to test whether de novo variants could contribute to this disease. We identified 20 de novo variants in 17 COS probands, which is consistent with the de novo mutation rate reported in the adult form of the disease. Interestingly, the missense de novo variants in COS have a high likelihood for pathogenicity and were enriched for genes that are less tolerant to variants. Among the genes found disrupted in our study, SEZ6, RYR2, GPR153, GTF2IRD1, TTBK1 and ITGA6 have been previously linked to neuronal function or to psychiatric disorders, and thus may be considered as COS candidate genes. |
| SCZ Keywords | schizophrenia |