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

406 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	44
Udgave nummer	3
Sider (fra-til)	247-50
Antal sider	4
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.1108
Status	Udgivet - mar. 2012

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10.1038/ng.1108

Citationsformater

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, bind 44, nr. 3, s. 247-50. https://doi.org/10.1038/ng.1108

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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.",

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AU - Lee, S Hong

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AU - Ripke, Stephan

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AU - Sullivan, Patrick F

AU - Goddard, Michael E

AU - Keller, Matthew C

AU - Visscher, Peter M

AU - Wray, Naomi R

AU - Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ)

AU - Hansen, Thomas Folkmann

AU - Ingason, Andrés

AU - Olsen, Line

AU - Rasmussen, Henrik Berg

AU - Werge, Thomas Mears

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AB - 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.

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

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