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Objectives: Schizophrenia is a highly inheritable disorder, but many aspects of its etiology and pathophysiology remain poorly understood. Recently, in the Han Chinese population, a SNP rs1635 located within the exon of the NKAPL gene (encoding NFKB activating protein-like) achieved genome-wide significance in schizophrenia., Methods: In order to find the causal variants of the NKAPL gene in schizophrenia, we searched for genetic variants in the promoter region, and exons (including both UTR ends) using direct sequencing in a sample of patients with schizophrenia (n=515) and non-psychotic controls (n=456), all Han Chinese from Taiwan, and conducted an association and rudimentary functional study., Results: We identified 5 common SNPs (defined as minor allele frequency (MAF)>0.01) in the NKAPL gene. In a case-control association analysis, the minor allele (A) of rs1635 was significantly more common among patients than controls (P=0.0003, OR=1.41, 95% CI=1.17-1.71). A haplotype analysis of the 5 common SNPs indicated a risk haplotype (rs12000C-rs1635A-rs9461446C-rs3734564G-rs1679709G) associated with schizophrenia (P=2.77e-005, OR=1.53, 95% CI=1.25-1.87). In addition, we identified 4 patient-specific rare SNPs (MAF<0.01) (c.137G>A, c.213G>A, c.752C>T (rs370337122), and c.844G>A (rs147161729)) within the NKAPL gene. In silico analysis demonstrated their functional impact on the protein; however, there was also 1 control-specific rare SNP (c.119G>A) detected within the NKAPL gene, indicating that the clinical relevance of these putatively pathological rare SNPs is not straightforward., Conclusions: This study suggested that rs1635 in the NKAPL gene appeared to play a role in conferring susceptibility to schizophrenia. In addition, some rare SNPs in the NKAPL gene with possibly damaging effects may be important in our patients. Our study provides genetic clues to indicate the involvement of NKAPL in schizophrenia., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Schizophrenia is a complex mental disorder with high degree of genetic influence in its etiology. Several recent studies revealed that copy number variations (CNVs) of genomic DNA contributed significantly to the genetic architecture of sporadic schizophrenia. This study aimed to investigate whether CNVs also contribute to the familial forms of schizophrenia. Using array-based comparative genomic hybridization technology, we searched for pathogenic CNV associated with schizophrenia in a sample of 60 index cases from multiplex schizophrenia families. We detected three inherited CNVs that were associated with schizophrenia in three families, including a microdeletion of ~4.4Mb at chromosome 6q12-q13, a microduplication of ~1Mb at chromosome 18q12.3, and an interstitial duplication of ~5Mb at chromosome 15q11.2-q13.1. Our data indicate that CNVs contribute to the genetic underpinnings of the familial forms of schizophrenia as well as of the sporadic form. As 15q11-13 duplication is a well-known recurrent CNV associated with autism in the literature, the detection of the 15q11.2-q13.1 duplication in our schizophrenia patients provides additional support to other studies reporting that schizophrenia is part of the clinical spectrum of 15q11-q13 duplication syndrome., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The association between autoimmune diseases and schizophrenia has rarely been systematically investigated., Aims: To investigate the association between schizophrenia and a variety of autoimmune diseases and to explore possible gender variation in any such association., Method: Taiwan's National Health Insurance Research Database was used to identify 10 811 hospital in-patients with schizophrenia and 108 110 age-matched controls. Univariate and multiple logistic regression analyses were performed, separately, to evaluate the association between autoimmune diseases and schizophrenia. We applied the false discovery rate to correct for multiple testing., Results: When compared with the control group, the in-patients with schizophrenia had an increased risk of Graves' disease (odds ratio (OR) = 1.32, 95% CI 1.04-1.67), psoriasis (OR = 1.48, 95% CI 1.07-2.04), pernicious anaemia (OR = 1.71, 95% CI 1.04-2.80), celiac disease (OR = 2.43, 95% CI 1.12-5.27) and hypersensitivity vasculitis (OR = 5.00, 95% CI 1.64-15.26), whereas a reverse association with rheumatoid arthritis (OR = 0.52, 95% CI 0.35-0.76) was also observed. Gender-specific variation was found for Sjögren syndrome, hereditary haemolytic anaemia, myasthenia gravis, polymyalgia rheumatica and dermatomyositis., Conclusions: Schizophrenia was associated with a greater variety of autoimmune diseases than was anticipated. Further investigation is needed to gain a better understanding of the aetiology of schizophrenia and autoimmune diseases.

Dysregulation of the immune response has been proposed as a precipitating factor of schizophrenia, and human leukocyte antigens (HLA) play a critical role in regulating the cascade of immunological reaction. Hence, many studies have investigated the relationship between the HLA system and schizophrenia. HLA is a complex gene family that contains several highly polymorphic genes, while the HLA-A gene is the most often studied gene to be associated with schizophrenia in the literature. A recent study reported that the interaction of the HLA-A10 allele and Chlamydial infection was highly associated with schizophrenia in a German population, which prompted us to investigate whether the HLA-A gene was also associated with schizophrenia in our population. Using a sequencing-based HLA typing method, we determined the HLA-A genotypes in 377 Han Chinese patients with schizophrenia (214 males, 163 females) and 321 non-psychotic Han Chinese control subjects (164 males, 157 females) from Taiwan. In total, 26 DNA-defined HLA-A alleles were identified in this sample. However, no significant differences of these allelic frequencies were found between the patients and the control subjects, suggesting that the HLA-A gene was unlikely a major risk factor of schizophrenia in this sample. As different populations have different HLA polymorphisms, an examination of the relationship of other HLA genes and schizophrenia in our population, with a larger sample size, is warranted in the future.

Background: The association between autoimmune diseases and schizophrenia has rarely been systematically investigated.Aims: To investigate the association between schizophrenia and a variety of autoimmune diseases and to explore possible gender variation in any such association.Method: Taiwan's National Health Insurance Research Database was used to identify 10 811 hospital in-patients with schizophrenia and 108 110 age-matched controls. Univariate and multiple logistic regression analyses were performed, separately, to evaluate the association between autoimmune diseases and schizophrenia. We applied the false discovery rate to correct for multiple testing.Results: When compared with the control group, the in-patients with schizophrenia had an increased risk of Graves' disease (odds ratio (OR) = 1.32, 95% CI 1.04-1.67), psoriasis (OR = 1.48, 95% CI 1.07-2.04), pernicious anaemia (OR = 1.71, 95% CI 1.04-2.80), celiac disease (OR = 2.43, 95% CI 1.12-5.27) and hypersensitivity vasculitis (OR = 5.00, 95% CI 1.64-15.26), whereas a reverse association with rheumatoid arthritis (OR = 0.52, 95% CI 0.35-0.76) was also observed. Gender-specific variation was found for Sjögren syndrome, hereditary haemolytic anaemia, myasthenia gravis, polymyalgia rheumatica and dermatomyositis.Conclusions: Schizophrenia was associated with a greater variety of autoimmune diseases than was anticipated. Further investigation is needed to gain a better understanding of the aetiology of schizophrenia and autoimmune diseases. [ABSTRACT FROM AUTHOR]