Copy number variants (CNVs) have been strongly implicated in the genetic
etiology of schizophrenia (SCZ). However, genome-wide investigation of
the contribution of CNV to risk has been hampered by limited sample
sizes. We sought to address this obstacle by applying a centralized
analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A
global enrichment of CNV burden was observed in cases (odds ratio (OR) =
1.11, P = 5.7 x 10(-15)), which persisted after excluding loci
implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden
was enriched for genes associated with synaptic function (OR = 1.68, P =
2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P =
7.3 x 10(-5)). Genome-wide significant evidence was obtained for eight
loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal
16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for
eight additional candidate susceptibility and protective loci, which
consisted predominantly of CNVs mediated by nonallelic homologous
recombination