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

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Harvard

Johnson, EC, Bjelland, DW, Howrigan, DP, Abdellaoui, A, Breen, G, Borglum, A, Cichon, S, Degenhardt, F, Forstner, AJ, Frank, J, Genovese, G, Heilmann-Heimbach, S, Herms, S, Hoffman, P, Maier, W, Mattheisen, M, Morris, D, Mowry, B, Müller-Mhysok, B, Neale, B, Nenadic, I, Nöthen, MM, O'Dushlaine, C, Rietschel, M, Ruderfer, DM, Rujescu, D, Schulze, TG, Simonson, MA, Stahl, E, Strohmaier, J, Witt, SH, Sullivan, PF, Keller, MC & Schizophrenia Working Group of the Psychiatric Genomics Consortium 2016, 'No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study', P L o S Genetics, bind 12, nr. 10, s. e1006343. https://doi.org/10.1371/journal.pgen.1006343

APA

Johnson, E. C., Bjelland, D. W., Howrigan, D. P., Abdellaoui, A., Breen, G., Borglum, A., Cichon, S., Degenhardt, F., Forstner, A. J., Frank, J., Genovese, G., Heilmann-Heimbach, S., Herms, S., Hoffman, P., Maier, W., Mattheisen, M., Morris, D., Mowry, B., Müller-Mhysok, B., ... Schizophrenia Working Group of the Psychiatric Genomics Consortium (2016). No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study. P L o S Genetics, 12(10), e1006343. https://doi.org/10.1371/journal.pgen.1006343

CBE

Johnson EC, Bjelland DW, Howrigan DP, Abdellaoui A, Breen G, Borglum A, Cichon S, Degenhardt F, Forstner AJ, Frank J, Genovese G, Heilmann-Heimbach S, Herms S, Hoffman P, Maier W, Mattheisen M, Morris D, Mowry B, Müller-Mhysok B, Neale B, Nenadic I, Nöthen MM, O'Dushlaine C, Rietschel M, Ruderfer DM, Rujescu D, Schulze TG, Simonson MA, Stahl E, Strohmaier J, Witt SH, Sullivan PF, Keller MC, Schizophrenia Working Group of the Psychiatric Genomics Consortium. 2016. No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study. P L o S Genetics. 12(10):e1006343. https://doi.org/10.1371/journal.pgen.1006343

MLA

Vancouver

Author

Johnson, Emma C ; Bjelland, Douglas W ; Howrigan, Daniel P ; Abdellaoui, Abdel ; Breen, Gerome ; Borglum, Anders ; Cichon, Sven ; Degenhardt, Franziska ; Forstner, Andreas J ; Frank, Josef ; Genovese, Giulio ; Heilmann-Heimbach, Stefanie ; Herms, Stefan ; Hoffman, Per ; Maier, Wolfgang ; Mattheisen, Manuel ; Morris, Derek ; Mowry, Bryan ; Müller-Mhysok, Betram ; Neale, Benjamin ; Nenadic, Igor ; Nöthen, Markus M ; O'Dushlaine, Colm ; Rietschel, Marcella ; Ruderfer, Douglas M ; Rujescu, Dan ; Schulze, Thomas G ; Simonson, Matthew A ; Stahl, Eli ; Strohmaier, Jana ; Witt, Stephanie H ; Sullivan, Patrick F ; Keller, Matthew C ; Schizophrenia Working Group of the Psychiatric Genomics Consortium. / No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study. I: P L o S Genetics. 2016 ; Bind 12, Nr. 10. s. e1006343.

Bibtex

@article{9c5c83e7249846278715e47074e93318,
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.",
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 {Schizophrenia Working Group of the Psychiatric Genomics Consortium} and Hansen, {Thomas Folkmann} and Werge, {Thomas Mears} and Line Olsen",
year = "2016",
month = oct,
doi = "10.1371/journal.pgen.1006343",
language = "English",
volume = "12",
pages = "e1006343",
journal = "Plos Genetics",
issn = "1553-7404",
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 - Schizophrenia Working Group of the Psychiatric Genomics Consortium

AU - Hansen, Thomas Folkmann

AU - Werge, Thomas Mears

AU - Olsen, Line

PY - 2016/10

Y1 - 2016/10

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.

U2 - 10.1371/journal.pgen.1006343

DO - 10.1371/journal.pgen.1006343

M3 - Journal article

C2 - 27792727

VL - 12

SP - e1006343

JO - Plos Genetics

JF - Plos Genetics

SN - 1553-7404

IS - 10

ER -

ID: 49759073