Genome-wide association analysis of age at onset in schizophrenia in a European-American sample

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 156B; no. 6; pp. 671 - 680
• Main Authors: Wang, Ke-Sheng, Liu, Xuefeng, Zhang, Qunyuan, Aragam, Nagesh, Pan, Yue
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2011; Wiley-Liss
• Subjects: Adult and adolescent clinical studies; Age; age at onset; Age of Onset; Association analysis; Biological and medical sciences; chromosome 4; Chromosomes, Human, Pair 4 - genetics; European Continental Ancestry Group - genetics; Female; Genetic Predisposition to Disease; gene × gender interaction; genome-wide association; Genome-Wide Association Study; Genotype; haplotype; Haplotypes; Humans; Medical genetics; Medical sciences; Mental disorders; Non-Fibrillar Collagens - genetics; Polymorphism, Single Nucleotide; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Regression analysis; Ryanodine receptors; Schizophrenia; Schizophrenia - genetics; Sex Factors; Single-nucleotide polymorphism; United States; North America; Europe; America; American; Gene interaction; Sample; Sex; Schizophrenia; European; Psychosis; Association; Age of onset; genome-wide association; Genome; Haplotype; age at onset; gene x gender interaction
• ISSN: 1552-4841; 1552-485X; 1552-485X
• DOI: 10.1002/ajmg.b.31209

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. © 2011 Wiley‐Liss, Inc.