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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 |
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