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.
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, 37614-1700, USA. wangk@etsu.edu
authors.forename: Ke-Sheng
authors.initials: KS
authors.lastname: Wang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Liu
authors.forename: Qunyuan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Nagesh
authors.initials: N
authors.lastname: Aragam
authors.forename: Yue
authors.initials: Y
authors.lastname: Pan
mesh_terms: D017668:Age of Onset; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D024041:Non-Fibrillar Collagens / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D012737:Sex Factors; D044465:White People / Q000235:genetics*
chemical_list: C456021:COL25A1 protein, human; D024041:Non-Fibrillar Collagens