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

By S. H. Lee, Teresa R. Decandia, S. Ripke, Jian Yang, Patrick F. Sullivan, Michael E. Goddard, Matthew C. Keller, P. M. Visscher, Naomi R. Wray. Nature Genetics, 2012

635 citations recorded by the source corpus.

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.

Subfields: Genetics

View Paper: https://www.semanticscholar.org/paper/c49adb6c2b226a4052aa0ff642f8cb0f54ca3fce

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Citations in the corpus

Successful Explanations Start with Accurate Descriptions: Questionnaire Items as Personality Markers for More Accurate Predictions (2018, background): “…of the GWAS results can often explain substantial amounts of variance in complex phenotypes such as intelligence (Davies et al., 2015), schizophrenia (Lee et al., 2012), BMI (Locke et al., 2015), or educational attainment (Okbay et al., 2016), even when applied to independent samples of people.”
Advancing the understanding of autism disease mechanisms through genetics (2016, positive): “Polygenic risk models ( Box 1 ) assume that there are many inherited variants contributing to ASD, each with a small effect that, in combination with environmental factors, result in an individual crossing a risk threshold to develop the disease 56–59 .”
Polygenic Modeling with Bayesian Sparse Linear Mixed Models (2012, methodology): “For example, the LMM approach from [22], which has recently become commonly used for PVE estimation (e.g. [24,44–46]), is equivalent to the assumption that eﬀect sizes are normally distributed, such that [Speciﬁcally, exact equivalence holds when the relatedness matrix in the LMM is computed from…”
A polygenic burden of rare disruptive mutations in schizophrenia (2014, background): “One striking outcome of these large-scale, genome-wide investigations is the degree of polygenicity, consistent with thousands of genes and noncoding loci harboring risk alleles (International Schizophrenia Consortium, 2008, 2009; Lee et al., 2012; Ripke et al, 2013; Malhotra & Sebat, 2012).”
Pitfalls of predicting complex traits from SNPs (2013, background): “For example, for both height and schizophrenia h 2 ~ 0.7–0.8 and ~ 0.5 for height 26 and 0.2–0.3 for schizophrenia 29, 30 .”
LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis (2016, methodology): “…the degree to which genetic variation affecting complex phenotypes is tagged by SNPs on genome-wide arrays (Yang et al, 2010; Yang et al, 2011; Lee et al, 2012), the degree to which this variation represents different functional categories and/or biological pathways (Yang et al. 2011; Gusev…”
DEMONSTRATING THE VALIDITY OF TWIN RESEARCH IN CRIMINOLOGY (2014, methodology): “GCTA also has been employed in assessments of schizophrenia (Lee et al., 2012) and other psychiatric disorders (Lee et al., 2013), components of personality (Vinkhuyzen et al., 2012), behavioral inhibition (McGue et al., 2013), and intelligence in both childhood (Benyamin et al., 2013) and…”
Power and Predictive Accuracy of Polygenic Risk Scores (2013, result): “These results are similar to a recent estimate using mixed modelling of the same data [27].”