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

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

In: PLoS Genetics, Vol. 12, No. 10, e1006343, 28.10.2016.

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Schizophrenia Working Group of the Psychiatric Genomics Consortium 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

APA

Schizophrenia Working Group of the Psychiatric Genomics Consortium (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

Vancouver

Schizophrenia Working Group of the Psychiatric Genomics Consortium. No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study. PLoS Genetics. 2016 Oct 28;12(10). e1006343. https://doi.org/10.1371/journal.pgen.1006343

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Schizophrenia Working Group of the Psychiatric Genomics Consortium. / No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study. In: PLoS Genetics. 2016 ; Vol. 12, No. 10.

Bibtex

@article{d55453f278bf4fb69a91923ffdbab17c,
title = "No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study",
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.",
keywords = "Consanguinity, Female, Genome, Human, Genome-Wide Association Study, Genomics, Homozygote, Humans, Male, Polymorphism, Single Nucleotide, Schizophrenia, Journal Article",
author = "Johnson, {Emma C} and Bjelland, {Douglas W} and Howrigan, {Daniel P} and Abdel Abdellaoui and Gerome Breen and Anders Borglum and Sven Cichon and Franziska Degenhardt and Forstner, {Andreas J} and Josef Frank and Giulio Genovese and Stefanie Heilmann-Heimbach and Stefan Herms and Per Hoffman and Wolfgang Maier and Manuel Mattheisen and Derek Morris and Bryan Mowry and Betram M{\"u}ller-Mhysok and Benjamin Neale and Igor Nenadic and N{\"o}then, {Markus M} and Colm O'Dushlaine and Marcella Rietschel and Ruderfer, {Douglas M} and Dan Rujescu and Schulze, {Thomas G} and Simonson, {Matthew A} and Eli Stahl and Jana Strohmaier and Witt, {Stephanie H} and Sullivan, {Patrick F} and Keller, {Matthew C} and Joanne Knight and {Schizophrenia Working Group of the Psychiatric Genomics Consortium}",
year = "2016",
month = oct,
day = "28",
doi = "10.1371/journal.pgen.1006343",
language = "English",
volume = "12",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "10",

}

RIS

TY - JOUR

T1 - No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

AU - Johnson, Emma C

AU - Bjelland, Douglas W

AU - Howrigan, Daniel P

AU - Abdellaoui, Abdel

AU - Breen, Gerome

AU - Borglum, Anders

AU - Cichon, Sven

AU - Degenhardt, Franziska

AU - Forstner, Andreas J

AU - Frank, Josef

AU - Genovese, Giulio

AU - Heilmann-Heimbach, Stefanie

AU - Herms, Stefan

AU - Hoffman, Per

AU - Maier, Wolfgang

AU - Mattheisen, Manuel

AU - Morris, Derek

AU - Mowry, Bryan

AU - Müller-Mhysok, Betram

AU - Neale, Benjamin

AU - Nenadic, Igor

AU - Nöthen, Markus M

AU - O'Dushlaine, Colm

AU - Rietschel, Marcella

AU - Ruderfer, Douglas M

AU - Rujescu, Dan

AU - Schulze, Thomas G

AU - Simonson, Matthew A

AU - Stahl, Eli

AU - Strohmaier, Jana

AU - Witt, Stephanie H

AU - Sullivan, Patrick F

AU - Keller, Matthew C

AU - Knight, Joanne

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

PY - 2016/10/28

Y1 - 2016/10/28

N2 - 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.

AB - 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.

KW - Consanguinity

KW - Female

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Genomics

KW - Homozygote

KW - Humans

KW - Male

KW - Polymorphism, Single Nucleotide

KW - Schizophrenia

KW - Journal Article

U2 - 10.1371/journal.pgen.1006343

DO - 10.1371/journal.pgen.1006343

M3 - Journal article

C2 - 27792727

VL - 12

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 10

M1 - e1006343

ER -