Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pgen.1006343
Title: No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study
Authors: 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.
M�ller-Mhysok B.
Neale B.
Nenadic I.
N�then M.M.
O?Dushlaine C.
Rietschel M.
Ruderfer D.M.
Rujescu D.
Schulze T.G.
Simonson M.A.
Stahl E.
Strohmaier J.
Witt S.H.
Ripke S.
Neale B.M.
Corvin A.
Walters J.T.R.
Farh K.-H.
Holmans P.A.
Lee P.
Bulik-Sullivan B.
Collier D.A.
Huang H.
Pers T.H.
Agartz I.
Agerbo E.
Albus M.
Alexander M.
Amin F.
Bacanu S.A.
Begemann M.
Belliveau R.A.
Bene J.
Bergen S.E.
Bevilacqua E.
Bigdeli T.B.
Black D.W.
Bruggeman R.
Buccola N.G.
Buckner R.L.
Byerley W.
Cahn W.
Cai G.
Campion D.
Cantor R.M.
Carr V.J.
Carrera N.
Catts S.V.
Chambert K.D.
Chan R.C.K.
Chen R.Y.L.
Chen E.Y.H.
Cheng W.
Cheung E.F.C.
Chong S.A.
Robert Cloninger C.
Cohen D.
Cohen N.
Cormican P.
Craddock N.
Crowley J.J.
Curtis D.
Davidson M.
Davis K.L.
Del Favero J.
Demontis D.
Dikeos D.
Dinan T.
Djurovic S.
Donohoe G.
Drapeau E.
Duan J.
Dudbridge F.
Durmishi N.
Eichhammer P.
Eriksson J.
Escott-Price V.
Essioux L.
Fanous A.H.
Farrell M.S.
Franke L.
Freedman R.
Freimer N.B.
Friedl M.
Friedman J.I.
Fromer M.
Georgieva L.
Giegling I.
Giusti-Rodr�guez P.
Godard S.
Goldstein J.I.
Golimbet V.
Gopal S.
Gratten J.
de Haan L.
Hammer C.
Hamshere M.L.
Hansen M.
Hansen T.
Haroutunian V.
Hartmann A.M.
Henskens F.A.
Hirschhorn J.N.
Hoffmann P.
Hofman A.
Hollegaard M.V.
Hougaard D.M.
Ikeda M.
Joa I.
Juli� A.
Kahn R.S.
Kalaydjieva L.
Karachanak-Yankova S.
Karjalainen J.
Kavanagh D.
Kennedy J.L.
Khrunin A.
Kim Y.
Klovins J.
Knowles J.A.
Konte B.
Kucinskas V.
Kucinskiene Z.A.
Kuzelova-Ptackova H.
K�hler A.K.
Laurent C.
Chee Keong J.L.
Hong Lee S.
Legge S.E.
Lerer B.
Li M.
Li T.
Liang K.-Y.
Lieberman J.
Limborska S.
Loughland C.M.
Lubinski J.
L�nnqvist J.
Macek M.
Magnusson P.K.E.
Maher B.S.
Mallet J.
Marsal S.
Mattingsdal M.
McCarley R.W.
McDonald C.
McIntosh A.M.
Meier S.
Meijer C.J.
Melegh B.
Melle I.
Mesholam-Gately R.I.
Metspalu A.
Michie P.T.
Milani L.
Milanova V.
Mokrab Y.
Mors O.
Murphy K.C.
Murray R.M.
Myin-Germeys I.
M�ller-Myhsok B.
Nelis M.
Nertney D.A.
Nestadt G.
Nicodemus K.K.
Nikitina-Zake L.
Nisenbaum L.
Nordin A.
O'Callaghan E.
O'Dushlaine C.
Anthony O'Neill F.
Oh S.-Y.
Olincy A.
Olsen L.
Van Os J.
Pantelis C.
Papadimitriou G.N.
Papiol S.
Parkhomenko E.
Pato M.T.
Paunio T.
Pejovic-Milovancevic M.
Perkins D.O.
Pietil�inen O.
Pimm J.
Pocklington A.J.
Powell J.
Price A.
Pulver A.E.
Purcell S.M.
Quested D.
Rasmussen H.B.
Reichenberg A.
Reimers M.A.
Richards A.L.
Roffman J.L.
Roussos P.
Salomaa V.
Sanders A.R.
Schall U.
Schubert C.R.
Schwab S.G.
Scolnick E.M.
Scott R.J.
Seidman L.J.
Shi J.
Sigurdsson E.
Silagadze T.
Silverman J.M.
Sim K. 
Slominsky P.
Smoller J.W.
So H.-C.
Spencer C.C.A.
Stahl E.A.
Stefansson H.
Steinberg S.
Stogmann E.
Straub R.E.
Strengman E.
Scott Stroup T.
Subramaniam M.
Suvisaari J.
Svrakic D.M.
Szatkiewicz J.P.
S�derman E.
Thirumalai S.
Toncheva D.
Tosato S.
Veijola J.
Waddington J.
Walsh D.
Wang D.
Wang Q.
Webb B.T.
Weiser M.
Wildenauer D.B.
Williams N.M.
Williams S.
Wolen A.R.
Wong E.H.M.
Wormley B.K.
Xi H.S.
Zai C.C.
Zheng X.
Zimprich F.
Wray N.R.
Stefansson K.
Visscher P.M.
Adolfsson R.
Andreassen O.A.
Blackwood D.H.R.
Bramon E.
Buxbaum J.D.
B?rglum A.D.
Darvasi A.
Domenici E.
Ehrenreich H.
Esko T.
Gejman P.V.
Gill M.
Gurling H.
Hultman C.M.
Iwata N.
Jablensky A.V.
J�nsson E.G.
Kendler K.S.
Kirov G.
Knight J.
Lencz T.
Levinson D.F.
Li Q.S.
Liu J.
Malhotra A.K.
McCarroll S.A.
McQuillin A.
Moran J.L.
Mortensen P.B.
Mowry B.J.
N�then M.M.
Ophoff R.A.
Owen M.J.
Palotie A.
Pato C.N.
Petryshen T.L.
Posthuma D.
Riley B.P.
Sham P.C.
Sklar P.
Clair D.S.
Weinberger D.R.
Wendland J.R.
Werge T.
Daly M.J.
O'Donovan M.C.
Sullivan P.F.
Keller M.C.
Keywords: Article
autozygosity
case control study
controlled study
educational status
genetic association
genetic parameters
genome analysis
human
inbreeding
major clinical study
molecular pathology
religion
replication study
runs of homozygosity
schizophrenia
single nucleotide polymorphism
social status
urban population
zygosity
consanguinity
female
genetics
genome-wide association study
genomics
homozygote
human genome
male
pathology
schizophrenia
Consanguinity
Female
Genome, Human
Genome-Wide Association Study
Genomics
Homozygote
Humans
Male
Polymorphism, Single Nucleotide
Schizophrenia
Issue Date: 2016
Citation: 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., M�ller-Mhysok B., Neale B., Nenadic I., N�then M.M., O?Dushlaine C., Rietschel M., Ruderfer D.M., Rujescu D., Schulze T.G., Simonson M.A., Stahl E., Strohmaier J., Witt S.H., Ripke S., Neale B.M., Corvin A., Walters J.T.R., Farh K.-H., Holmans P.A., Lee P., Bulik-Sullivan B., Collier D.A., Huang H., Pers T.H., Agartz I., Agerbo E., Albus M., Alexander M., Amin F., Bacanu S.A., Begemann M., Belliveau R.A., Bene J., Bergen S.E., Bevilacqua E., Bigdeli T.B., Black D.W., Bruggeman R., Buccola N.G., Buckner R.L., Byerley W., Cahn W., Cai G., Campion D., Cantor R.M., Carr V.J., Carrera N., Catts S.V., Chambert K.D., Chan R.C.K., Chen R.Y.L., Chen E.Y.H., Cheng W., Cheung E.F.C., Chong S.A., Robert Cloninger C., Cohen D., Cohen N., Cormican P., Craddock N., Crowley J.J., Curtis D., Davidson M., Davis K.L., Del Favero J., Demontis D., Dikeos D., Dinan T., Djurovic S., Donohoe G., Drapeau E., Duan J., Dudbridge F., Durmishi N., Eichhammer P., Eriksson J., Escott-Price V., Essioux L., Fanous A.H., Farrell M.S., Franke L., Freedman R., Freimer N.B., Friedl M., Friedman J.I., Fromer M., Georgieva L., Giegling I., Giusti-Rodr�guez P., Godard S., Goldstein J.I., Golimbet V., Gopal S., Gratten J., de Haan L., Hammer C., Hamshere M.L., Hansen M., Hansen T., Haroutunian V., Hartmann A.M., Henskens F.A., Hirschhorn J.N., Hoffmann P., Hofman A., Hollegaard M.V., Hougaard D.M., Ikeda M., Joa I., Juli� A., Kahn R.S., Kalaydjieva L., Karachanak-Yankova S., Karjalainen J., Kavanagh D., Kennedy J.L., Khrunin A., Kim Y., Klovins J., Knowles J.A., Konte B., Kucinskas V., Kucinskiene Z.A., Kuzelova-Ptackova H., K�hler A.K., Laurent C., Chee Keong J.L., Hong Lee S., Legge S.E., Lerer B., Li M., Li T., Liang K.-Y., Lieberman J., Limborska S., Loughland C.M., Lubinski J., L�nnqvist J., Macek M., Magnusson P.K.E., Maher B.S., Mallet J., Marsal S., Mattingsdal M., McCarley R.W., McDonald C., McIntosh A.M., Meier S., Meijer C.J., Melegh B., Melle I., Mesholam-Gately R.I., Metspalu A., Michie P.T., Milani L., Milanova V., Mokrab Y., Mors O., Murphy K.C., Murray R.M., Myin-Germeys I., M�ller-Myhsok B., Nelis M., Nertney D.A., Nestadt G., Nicodemus K.K., Nikitina-Zake L., Nisenbaum L., Nordin A., O'Callaghan E., O'Dushlaine C., Anthony O'Neill F., Oh S.-Y., Olincy A., Olsen L., Van Os J., Pantelis C., Papadimitriou G.N., Papiol S., Parkhomenko E., Pato M.T., Paunio T., Pejovic-Milovancevic M., Perkins D.O., Pietil�inen O., Pimm J., Pocklington A.J., Powell J., Price A., Pulver A.E., Purcell S.M., Quested D., Rasmussen H.B., Reichenberg A., Reimers M.A., Richards A.L., Roffman J.L., Roussos P., Salomaa V., Sanders A.R., Schall U., Schubert C.R., Schwab S.G., Scolnick E.M., Scott R.J., Seidman L.J., Shi J., Sigurdsson E., Silagadze T., Silverman J.M., Sim K., Slominsky P., Smoller J.W., So H.-C., Spencer C.C.A., Stahl E.A., Stefansson H., Steinberg S., Stogmann E., Straub R.E., Strengman E., Scott Stroup T., Subramaniam M., Suvisaari J., Svrakic D.M., Szatkiewicz J.P., S�derman E., Thirumalai S., Toncheva D., Tosato S., Veijola J., Waddington J., Walsh D., Wang D., Wang Q., Webb B.T., Weiser M., Wildenauer D.B., Williams N.M., Williams S., Wolen A.R., Wong E.H.M., Wormley B.K., Xi H.S., Zai C.C., Zheng X., Zimprich F., Wray N.R., Stefansson K., Visscher P.M., Adolfsson R., Andreassen O.A., Blackwood D.H.R., Bramon E., Buxbaum J.D., B?rglum A.D., Darvasi A., Domenici E., Ehrenreich H., Esko T., Gejman P.V., Gill M., Gurling H., Hultman C.M., Iwata N., Jablensky A.V., J�nsson E.G., Kendler K.S., Kirov G., Knight J., Lencz T., Levinson D.F., Li Q.S., Liu J., Malhotra A.K., McCarroll S.A., McQuillin A., Moran J.L., Mortensen P.B., Mowry B.J., N�then M.M., Ophoff R.A., Owen M.J., Palotie A., Pato C.N., Petryshen T.L., Posthuma D., Riley B.P., Sham P.C., Sklar P., Clair D.S., Weinberger D.R., Wendland J.R., Werge T., Daly M.J., O'Donovan M.C., Sullivan P.F., Keller M.C. (2016). No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study. PLoS Genetics 12 (10) : e1006343. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pgen.1006343
Rights: Attribution 4.0 International
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. ? 2016 Johnson et al.
Source Title: PLoS Genetics
URI: https://scholarbank.nus.edu.sg/handle/10635/161903
ISSN: 15537390
DOI: 10.1371/journal.pgen.1006343
Rights: Attribution 4.0 International
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pgen_1006343.pdf1.86 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

9
checked on Jun 15, 2021

Page view(s)

156
checked on Jun 12, 2021

Download(s)

1
checked on Jun 12, 2021

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons