PLoS ONE (Jan 2012)

Genome-wide association study of treatment refractory schizophrenia in Han Chinese.

  • 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

DOI
https://doi.org/10.1371/journal.pone.0033598
Journal volume & issue
Vol. 7, no. 3
p. e33598

Abstract

Read online

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.