Study Report

Reference	Papiol, S.,2004 PMID: 14985387
Citation	Papiol, S., A. Rosa, et al. (2004). "Interleukin-1 cluster is associated with genetic risk for schizophrenia and bipolar disorder." J Med Genet 41(3): 219-223.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	78 schizophrenic patients, 88 bipolar disorder patients, and 176 healthy controls.
SNP/Region/Marker Size	2 variants
Predominant Ethnicity
Population	Spanish
Age Group	Adults : Mean age(SD)(year):44.8(14.9) for BD patients,31.1(7.5) for SZ patients and 39.82(10.35) for controls

Sample Diagnosis	DSM
Sample Status	The schizophrenic patients' sample consisted of 78 unrelated DSM-IV diagnosed patients from two public mental health centres in Barcelona: the Mental Health Service of the Eixample district (n=38) and the Institut Municipal d'Urge`ncies Psiquia`triques (IMPU)(n=40). The mean evolution time ipatients since the first episode was 9.9 years (SD 7.8) and the mean age at onset, defined as the age at which psychotic symptoms first became evident, was 21.2 years (SD 4.6). A total of 88 unrelated patients meeting the DSM-III-R criteria for bipolar disorder recruited from Cl?_nica Mental Santa Coloma of Barcelona constituted the bipolar disorder patients' sample. The mean evolution time in patients since the first episode was 15.9 years (SD 12.9) and the mean age at onset was 29.5 years (SD 11.6).According to this interview, 67% of the sample showed a positive family history of severe mental disorder(schizophrenia, bipolar disorder, and/or severe major depression) in at least a first degree relative. This sample consistedof a group of inpatients presenting an extremely severe outcome (see Valle`s et al11 for additional details about the clinical profile of this sample and its psychiatric familial morbid risk).The control group consisted of 176 healthy individuals recruited from the catchment area of the hospitals involved in this study and can be considered to be representative of the general population of Barcelona. Additionally, the Spanish version of the 28-item General Health Questionnaire (GHQ)33 was used to assess current mental condition. All controls and patients showing a positive personal history of neurological disease, cancer, diabetes, or drug or alcohol abuse were excluded from the study. All cases and controls were of white Spanish origin, shared similar sociodemographic profiles and were comparable as regards the geographical origin of their families.
Technique	genotyping
Statistical Method	Simple X2 tests of independence were also performed to confirm the presence or absence of allele or genotype associations. The ARLEQUIN program was used to estimate the haplotypes and their frequencies according to genotype information (expectation maximisation (EM) algorithm) as well as to determine the statistical significance of linkage disequilibrium.
Result Summary	A significant excess of the haplotypic combination 2511 allele*1/VNTR allele*2 was found both in schizophrenic (P = 0.0015; OR= 2.49 (95% confidence interval (CI): 1.33 to 4.64)) and bipolar patients(P = 0.004; OR= 2.26 (95% CI: 1.22 to 4.17)) when compared with controls. The highest risk conferred by this risk haplotype was detected in bipolar patients with a family history of schizophrenia, bipolar disorder, or severe major depression (P = 0.00009; OR = 3.18(95% CI: 1.66 to 6.05)).IL-1 cluster genetic variability may represent a shared genetic susceptibility factor both for schizophrenia and bipolar disorder.