Study Report

Reference	Steinberg, S.,2012 PMID: 23164818
Citation	Steinberg, S., et al. (2012). "Common variant at 16p11.2 conferring risk of psychosis." Mol Psychiatry.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Genome-wide association study
Sample Size	Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls)
Predominant Ethnicity

Sample Diagnosis	DSM
Sample Status	The genome-wide typed (SGENE-plus; 2663 cases and 13 498 controls) and meta-analysis (SGENE-plus_ISC_MGS) samples (in total, 7946 cases and 19 036 controls) used here were identical to those used in our previous schizophrenia GWA study and meta-analysis.15 The primary psychosis follow-up samples employed consisted of follow-up samples from our previous GWA follow-up study (9246 schizophrenia cases and 22 356 controls),14 plus an additional 9337 psychosis cases (1535 schizophrenia, 7469 bipolar disorder and 333 related psychoses) and 46 968 controls/unaffected family members. The primary follow-up samples were genotyped or imputed for all follow-up markers. The secondary followup samples consisted of 1014 cases and 1144 controls from the Go¬ ttingen Research Association for Schizophrenia34,35 study. These samples, which also had been used for secondary follow-up in our previous GWA follow-up study,14 were genotyped for SNPs that were genome-wide significant in the combined meta-analysis and primary follow-up samples.
Technique	Genotyping was carried out using Illumina (San Diego, CA, USA) and Affymetrix genome-wide arrays (Santa Clara, CA, USA), Nanogen (San Diego, CA, USA) Centaurus assays, Taqman assays, the Sequenom MassArray iPLEX genotyping system (San Diego, CA, USA) and the Roche LightCycler480 system (Mannheim, Germany)
Statistical Method	Association analysis was carried out using UNPHASED.
Result Summary	Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 x 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).