title: Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs.
abstract: Schizophrenia is a complex disorder caused by both genetic and environmental factors. Using 9,087 affected individuals, 12,171 controls and 915,354 imputed SNPs from the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC-SCZ), we estimate that 23% (s.e. = 1%) of variation in liability to schizophrenia is captured by SNPs. We show that a substantial proportion of this variation must be the result of common causal variants, that the variance explained by each chromosome is linearly related to its length (r = 0.89, P = 2.6 × 10(-8)), that the genetic basis of schizophrenia is the same in males and females, and that a disproportionate proportion of variation is attributable to a set of 2,725 genes expressed in the central nervous system (CNS; P = 7.6 × 10(-8)). These results are consistent with a polygenic genetic architecture and imply more individual SNP associations will be detected for this disease as sample size increases.
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Australia.
authors.forename: S Hong
authors.initials: SH
authors.lastname: Lee
authors.forename: Teresa R
authors.initials: TR
authors.lastname: DeCandia
authors.forename: Stephan
authors.initials: S
authors.lastname: Ripke
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
authors.forename: Michael E
authors.initials: ME
authors.lastname: Goddard
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Keller
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
mesh_terms: D000704:Analysis of Variance; D002490:Central Nervous System / Q000378:metabolism; D002877:Chromosomes, Human / Q000235:genetics*; D003198:Computer Simulation; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D016013:Likelihood Functions; D016014:Linear Models; D008297:Male; D008957:Models, Genetic; D058977:Molecular Sequence Annotation; D020412:Multifactorial Inheritance / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*