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Genome‐wide association analysis of age at onset in schizophrenia in a European‐American sample
Author(s) -
Wang KeSheng,
Liu Xuefeng,
Zhang Qunyuan,
Aragam Nagesh,
Pan Yue
Publication year - 2011
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31209
Subject(s) - single nucleotide polymorphism , genetic association , snp , genetics , genome wide association study , association test , biology , gene , schizophrenia (object oriented programming) , medicine , genotype , psychiatry
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.