Independent component analysis of SNPs reflects polygenic risk scores for schizophrenia

Jiayu Chen, Vince Daniel Calhoun, Godfrey D. Pearlson, Nora I. Perrone-Bizzozero, Jessica A. Turner, Stefan Ehrlich, Beng Choon Ho, Jingyu Liu

Research output: Contribution to journalArticle

Abstract

Schizophrenia is a psychiatric disorder with high heritability. Recent genome-wide association studies have provided a list of risk loci reliably derived from unprecedentedly large samples. However, further delineation of the diagnosis-associated susceptibility variants is needed to better characterize the genetic architecture given the disease's complex nature. In this sense, a data-driven approach might hold promise for identifying functionally related clusters of genetic variants that might not be captured by hypothesis-based models. In the current study, independent component analysis (ICA) was applied to the Psychiatric Genomics Consortium's schizophrenia-related single nucleotide polymorphisms (SNPs) in 104 schizophrenia patients and 142 healthy controls of European Ancestry. We found that, for 13 out of 16 extracted independent components, the associated loadings correlated highly (r. > 0.5) with the polygenic risk scores for SZ of the corresponding SNPs. These correlations were likely not inflated by the linkage disequilibrium structure (permutation p. <. 0.001). In brief, we demonstrate an example of ICA analysis on SNP data yielding functionally meaningful clusters, which motivates further application of data-driven approaches as a complimentary tool for hypothesis-based methods to enrich our knowledge on the genetic basis of complex disorders.

Original languageEnglish (US)
JournalSchizophrenia Research
DOIs
StateAccepted/In press - Jul 5 2016
Externally publishedYes

Fingerprint

Single Nucleotide Polymorphism
Schizophrenia
Psychiatry
Genome-Wide Association Study
Linkage Disequilibrium
Genomics

Keywords

  • ICA
  • PGC
  • Polygenic risk score
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Chen, J., Calhoun, V. D., Pearlson, G. D., Perrone-Bizzozero, N. I., Turner, J. A., Ehrlich, S., ... Liu, J. (Accepted/In press). Independent component analysis of SNPs reflects polygenic risk scores for schizophrenia. Schizophrenia Research. https://doi.org/10.1016/j.schres.2016.09.011

Independent component analysis of SNPs reflects polygenic risk scores for schizophrenia. / Chen, Jiayu; Calhoun, Vince Daniel; Pearlson, Godfrey D.; Perrone-Bizzozero, Nora I.; Turner, Jessica A.; Ehrlich, Stefan; Ho, Beng Choon; Liu, Jingyu.

In: Schizophrenia Research, 05.07.2016.

Research output: Contribution to journalArticle

Chen, Jiayu ; Calhoun, Vince Daniel ; Pearlson, Godfrey D. ; Perrone-Bizzozero, Nora I. ; Turner, Jessica A. ; Ehrlich, Stefan ; Ho, Beng Choon ; Liu, Jingyu. / Independent component analysis of SNPs reflects polygenic risk scores for schizophrenia. In: Schizophrenia Research. 2016.
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