No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

Schizophrenia Working Group of the Psychiatric Genomics Consortium, Jeffrey Lieberman

Research output: Contribution to journalArticle

Abstract

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest.

Original languageEnglish (US)
Article numbere1006343
JournalPLoS Genetics
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

inbreeding
homozygosity
Schizophrenia
genome
Inbreeding
genomics
socioeconomic status
etiology
Genome
Genomics
Psychiatry
polymorphism
education
disease diagnosis
Social Class
single nucleotide polymorphism
Single Nucleotide Polymorphism
effect
schizophrenia
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Schizophrenia Working Group of the Psychiatric Genomics Consortium, & Lieberman, J. (2016). No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study. PLoS Genetics, 12(10), [e1006343]. https://doi.org/10.1371/journal.pgen.1006343

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study. / Schizophrenia Working Group of the Psychiatric Genomics Consortium; Lieberman, Jeffrey.

In: PLoS Genetics, Vol. 12, No. 10, e1006343, 01.10.2016.

Research output: Contribution to journalArticle

Schizophrenia Working Group of the Psychiatric Genomics Consortium & Lieberman, J 2016, 'No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study', PLoS Genetics, vol. 12, no. 10, e1006343. https://doi.org/10.1371/journal.pgen.1006343
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Lieberman J. No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study. PLoS Genetics. 2016 Oct 1;12(10). e1006343. https://doi.org/10.1371/journal.pgen.1006343
Schizophrenia Working Group of the Psychiatric Genomics Consortium ; Lieberman, Jeffrey. / No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study. In: PLoS Genetics. 2016 ; Vol. 12, No. 10.
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