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

Abstract

<div><p>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 (<em>P</em> = 3.04×10⁻⁷) and rs11265461 (<em>P</em> = 1.94×10⁻⁷) are adjacent to signaling lymphocytic activation molecule family member 1 (<em>SLAMF1</em>); rs4699030 (<em>P</em> = 1.94×10⁻⁶) and rs230529 (<em>P</em> = 1.74×10⁻⁷) are located in the gene nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (<em>NFKB1</em>); and rs13049286 (<em>P</em> = 3.05×10⁻⁵) and rs3827219 (<em>P</em> = 1.66×10⁻⁵) fall in receptor-interacting serine/threonine-protein kinase 4 (<em>RIPK4</em>). One isolated single nucleotide polymorphism (SNP), rs739617 (<em>P</em> = 3.87×10⁻⁵) was also identified to be associated with TRS. The -94delATTG allele (rs28362691) located in the promoter region of <em>NFKB1</em> was identified by resequencing and was found to associate with TRS (<em>P</em> = 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 <em>NFKB1</em> might be involved in the development of TRS.</p> </div