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Genome-Wide Association Study of Treatment Refractory Schizophrenia in Han Chinese

Author

Listed:
  • Ying-Jay Liou
  • Hui-Hung Wang
  • Ming-Ta Michael Lee
  • Sheng-Chang Wang
  • Hung-Lun Chiang
  • Cheng-Chung Chen
  • Ching-Hua Lin
  • Ming-Shun Chung
  • Chien-Cheng Kuo
  • Ding-Lieh Liao
  • Ching-Kuan Wu
  • Chih-Min Liu
  • Yu-Li Liu
  • Hai-Gwo Hwu
  • I-Ching Lai
  • Shih-Jen Tsai
  • Chia-Hsiang Chen
  • Hui-Fen Liu
  • Yi-Chun Chou
  • Chien-Hsiun Chen
  • Yuan-Tsong Chen
  • Chen-Jee Hong
  • Jer-Yuarn Wu

Abstract

We report the first genome-wide association study of a joint analysis using 795 Han Chinese individuals with treatment-refractory schizophrenia (TRS) and 806 controls. Three loci showed suggestive significant association with TRS were identified. These loci include: rs10218843 (P = 3.04×10−7) and rs11265461 (P = 1.94×10−7) are adjacent to signaling lymphocytic activation molecule family member 1 (SLAMF1); rs4699030 (P = 1.94×10−6) and rs230529 (P = 1.74×10−7) are located in the gene nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1); and rs13049286 (P = 3.05×10−5) and rs3827219 (P = 1.66×10−5) fall in receptor-interacting serine/threonine-protein kinase 4 (RIPK4). One isolated single nucleotide polymorphism (SNP), rs739617 (P = 3.87×10−5) was also identified to be associated with TRS. The -94delATTG allele (rs28362691) located in the promoter region of NFKB1 was identified by resequencing and was found to associate with TRS (P = 4.85×10−6). The promoter assay demonstrated that the -94delATTG allele had a significant lower promoter activity than the -94insATTG allele in the SH-SY5Y cells. This study suggests that rs28362691 in NFKB1 might be involved in the development of TRS.

Suggested Citation

  • Ying-Jay Liou & Hui-Hung Wang & Ming-Ta Michael Lee & Sheng-Chang Wang & Hung-Lun Chiang & Cheng-Chung Chen & Ching-Hua Lin & Ming-Shun Chung & Chien-Cheng Kuo & Ding-Lieh Liao & Ching-Kuan Wu & Chih-, 2012. "Genome-Wide Association Study of Treatment Refractory Schizophrenia in Han Chinese," PLOS ONE, Public Library of Science, vol. 7(3), pages 1-10, March.
  • Handle: RePEc:plo:pone00:0033598
    DOI: 10.1371/journal.pone.0033598
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