title: Rare and common variants at 16p11.2 are associated with schizophrenia.
abstract: 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 (29.6-30.2Mb, 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.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China. Electronic address: limingkiz@mail.kiz.ac.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China. Electronic address: xiaoxiao2@mail.kiz.ac.cn.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
mesh_terms: D058674:Chromosome Duplication; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D012559:Schizophrenia / Q000235:genetics*
keywords: 16p11.2 duplication; Copy number variation; GWAS; Schizophrenia