Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs

S Hong Lee; Teresa R DeCandia; Stephan Ripke; Jian Yang; Patrick F Sullivan; Michael E Goddard; Matthew C Keller; Peter M Visscher; Naomi R Wray; Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ); Thomas Folkmann Hansen; Andrés Ingason; Line Olsen; Henrik Berg Rasmussen; Thomas Mears Werge

doi:10.1038/ng.1108

Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs

S Hong Lee, Teresa R DeCandia, Stephan Ripke, Jian Yang, Patrick F Sullivan, Michael E Goddard, Matthew C Keller, Peter M Visscher, Naomi R Wray, Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), Thomas Folkmann Hansen, Andrés Ingason, Line Olsen, Henrik Berg Rasmussen, Thomas Mears Werge

474 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	44
Issue number	3
Pages (from-to)	247-50
Number of pages	4
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.1108
Publication status	Published - 2012

Keywords

Analysis of Variance
Central Nervous System
Chromosomes, Human
Computer Simulation
Female
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Humans
Likelihood Functions
Linear Models
Male
Models, Genetic
Molecular Sequence Annotation
Multifactorial Inheritance
Polymorphism, Single Nucleotide
Schizophrenia

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Lee, S. H., DeCandia, T. R., Ripke, S., Yang, J., Sullivan, P. F., Goddard, M. E., Keller, M. C., Visscher, P. M., Wray, N. R., Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), Hansen, T. F., Ingason, A., Olsen, L., Rasmussen, H. B., & Werge, T. M. (2012). Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nature Genetics, 44(3), 247-50. https://doi.org/10.1038/ng.1108

Lee, SH, DeCandia, TR, Ripke, S, Yang, J, Sullivan, PF, Goddard, ME, Keller, MC, Visscher, PM, Wray, NR, Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), Hansen, TF , Ingason, A, Olsen, L, Rasmussen, HB & Werge, TM 2012, 'Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs', Nature Genetics, vol. 44, no. 3, pp. 247-50. https://doi.org/10.1038/ng.1108

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Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs

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