Research Article

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

  1. Ke-Sheng Wang1,*,
  2. Xuefeng Liu1,
  3. Qunyuan Zhang2,
  4. Nagesh Aragam1,
  5. Yue Pan3

Article first published online: 17 JUN 2011

DOI: 10.1002/ajmg.b.31209

Issue

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

Volume 156, Issue 6, pages 671–680, September 2011

Additional Information

How to Cite

Wang, K.-S., Liu, X., Zhang, Q., Aragam, N. and Pan, Y. (2011), Genome-wide association analysis of age at onset in schizophrenia in a European-American sample. Am. J. Med. Genet., 156: 671–680. doi: 10.1002/ajmg.b.31209

Author Information

  1. 1

    Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, Tennessee

  2. 2

    Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri

  3. 3

    Department of Mathematics and Statistics, College of Arts and Sciences, East Tennessee State University, Johnson City, Tennessee

*Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, PO Box 70259, Lamb Hall, Johnson City, TN 37614-1700.

  1. †

    How to Cite this Article: Wang K-S, Liu X, Zhang Q, Aragam N, Pan Y. 2011. Genome-wide Association Analysis of Age at Onset in Schizophrenia in a European-American Sample. Am J Med Genet Part B 156:671–680.

Publication History

  1. Issue published online: 10 AUG 2011
  2. Article first published online: 17 JUN 2011
  3. Manuscript Accepted: 26 MAY 2011
  4. Manuscript Received: 22 JUL 2010

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Keywords:

  • schizophrenia;
  • age at onset;
  • genome-wide association;
  • gene × gender interaction;
  • haplotype

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. © 2011 Wiley-Liss, Inc.

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