Rare and common variants at 16p11.2 are associated with schizophrenia

Recent studies suggest that both common and rare variants are involved in the genetic risk of schizophrenia. Using a Cochran-Mantel-Haenszel (CMH) adjusted meta-analysis in 36,676 schizophrenia patients and 48,331 healthy controls from 24 independent samples, we identify the microduplications at 16p11.2 locus (29.6-30.2 Mb, hg19) to be strongly associated with the illness (P value < 2.2 × 10− 16, CHM-adjusted OR = 10.79). The frequency of this microduplication is significantly higher in schizophrenia patients (0.267%) comparing to healthy controls (0.025%). Further, using the largest published genome-wide association study (GWAS) data (36,989 cases and 113,075 controls), we show that common variants at the 16p11.2 locus are also significantly associated with schizophrenia (e.g., rs12691307, P value = 4.55 × 10− 11, OR = 1.073). These results confirm the link between 16p11.2 genomic region and genetic risk of schizophrenia.