Study Report

Reference	Liu, J,2011(a) PMID: 21040781
Citation	Liu, J., J. Li, et al. (2011). "CTLA-4 confers a risk of recurrent schizophrenia, major depressive disorder and bipolar disorder in the Chinese Han population." Brain Behav Immun 25(3): 429-433.
Disease Type	Bipolar Disorder & Schizophrenia & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	1140 unrelated schizophrenia cases,1140 unrelated major depressive disorder cases, 1140 unrelated bipolar disorder cases and 1140 normal controls
SNP/Region/Marker Size	6 SNPs
Predominant Ethnicity	Mongloid
Population	Chinese
Gender	Male/female:623/517 in BD patients ,635/505 in SZ patients,483/652 in MDD patients and 374/766 in controls
Age Group	Adults : Mean age(SD)(year):36.6(13.8) in BD patients ,35.4 (7.2) in SZ patients, 35.1(11.6) in MDD patients and 58.7(9.9) in controls

Sample Diagnosis	DSM
Sample Status	All subjects gave informed consent for the genetic analysis, which was reviewed and approved by the ethical committee of the Human Genetics Center in Shanghai. This sample set recruited from the Chinese Han population. All subjects were born in Shanghai. All patients were chosen on the basis of interview data and hospital case notes according to the following criteria: (1) Were diagnosed strictly according to DSM-IV criteria (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) with two experienced psychiatrists reaching consensus on the basis of unstructured interviews and review of medical records; (2) No physical disease, history of traumatic brain injury, immune related diseases or other diseases by detailed medical examination; (3) no drug abuse or alcoholism; (4) not been treated with any psychotropic medicine before they were diagnosed; (5) all the patients were at the status of onset. All the healthy controls were randomly selected from Shanghai local citizens. Volunteers who replied to a written invitation completed evaluation of medical history, supplemented by questions about psychosis, and other major complex diseases. Before collecting their blood, a face to face interview and physical examination including height, weight, blood pressure, etc. were carried out. Practice lists were screened for potentially suitable volunteers by exclusion of subjects with major mental illness in individual themselves and first degree relatives or use of neuroleptic medication. Moreover, controls were excluded if they were clearly diagnosed for other diseases, such as cancer, diabetes, immune related diseases, etc. One case/control study using this sample has been published (Li et al., 2010).
Technique	genotyping
Statistical Method	Hardy-Weinberg equilibrium testing (HWE), P-value computations [P > 0.05], in both the healthy control and patient groups, the allele and genotype frequency analysis were all performed on SHEsis software () (Shi and He 2005; Li et al., 2009). Both allelic and genotypic data of each disorder were performed 10,000 permutations (accessed with nominal permutation) based on Westfall and Young correction. All tests were two-tailed and statistical significance was assumed at P < 0.05.
Result Summary	We found that rs231779 conferred a risk for schizophrenia (P(allele)=0.0003, P(genotype)=0.0016), major depressive disorder (P(allele)=0.0006, P(genotype)=0.0026) and bipolar disorder (P(allele)=0.0004, P(genotype)=0.0018). In addition, rs231777 and rs16840252 had a significant association with schizophrenia (rs231777: P(allele)=0.0201, rs16840252: P(allele)=0.0081, P(genotype)=0.0117), and rs231777 had significant association with bipolar disorder (rs231777: P(allele)=0.0199). However, after 10,000 permutations, only rs231779 remained significant (schizophrenia: P(allele)=0.0010, P(genotype)=0.0145, major depressive disorder: P(allele)=0.0010, P(genotype)=0.0201, bipolar disorder: P(allele)=0.0008, P(genotype)=0.0125). Our results suggest that shared common risk factors for schizophrenia, major depressive disorder and bipolar disorder exist in the CTLA-4 gene in the Chinese Han population.