Type

Journal Article

Authors

Matthew C Keller
Patrick F Sullivan
Stephanie H Witt
Jana Strohmaier
Eli Stahl
Matthew A Simonson
Thomas G Schulze
Dan Rujescu
Douglas M Ruderfer
Marcella Rietschel
and 24 others

Subjects

Psychiatry

Topics
homozygote male epidemiology pathology case control humans genome human schizophrenia phase ii association study female replication genomics outcome measures socioeconomic status consanguinity runs of homozygosity genetics genome wide association study polymorphism single nucleotide

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study (2016)

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 (? = 16.1, CI(?) = [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 (? = 4.86,CI(?) = [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.
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Full list of authors on original publication

Matthew C Keller, Patrick F Sullivan, Stephanie H Witt, Jana Strohmaier, Eli Stahl, Matthew A Simonson, Thomas G Schulze, Dan Rujescu, Douglas M Ruderfer, Marcella Rietschel and 24 others

Experts in our system

1
P F Sullivan
Trinity College Dublin
Total Publications: 12
 
2
Dan Rujescu
Trinity College Dublin
Total Publications: 20
 
3
Marcella Rietschel
Trinity College Dublin
Total Publications: 39