No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study
Creators: name: Stogmann, Elisabeth
name: Liang, Kung-Yee
name: Hoffman, Per
name: Herms, Stefan
name: Donohoe, Gary
name: Kalaydjieva, Luba
name: Waddington, John
name: Buckner, Randy L.
name: Bevilacqua, Elizabeth
name: Mowry, Bryan J.
name: Powell, John
name: Mattheisen, Manuel
name: Jablensky, Assen V.
name: Dinan, Timothy
name: Kennedy, James L.
name: Hammer, Christian
name: Stefansson, Kari
name: Fromer, Menachem
name: Mesholam-Gately, Raquelle I.
name: Scott, Rodney J.
name: Chong, Siow Ann
name: Milani, Lili
name: Wang, Dai
name: Stahl, Eli A.
name: Agartz, Ingrid
name: Meijer, Carin J.
name: Gopal, Srihari
name: Price, Alkes
name: Milanova, Vihra
name: Stahl, Eli
name: Farh, Kai-How
name: Murphy, Kieran C.
name: Frank, Josef
name: Palotie, Aarno
name: Cohen, David
name: Bene, Judit
name: Slominsky, Petr
name: Seidman, Larry J.
name: Demontis, Ditte
name: Olsen, Line
name: Giusti-Rodríguez, Paola
name: Pulver, Ann E.
name: Andreassen, Ole A.
name: Toncheva, Draga
name: Kuzelova-Ptackova, Hana
name: Knowles, James A.
name: Sham, Pak C.
name: Davis, Kenneth L.
name: Strohmaier, Jana
name: Cormican, Paul
name: Bacanu, Silviu A.
name: Nenadic, Igor
name: O'Donovan, Michael C.
name: Haroutunian, Vahram
name: O'Dushlaine, Colm
name: Genovese, Giulio
name: Mortensen, Preben B.
name: Friedl, Marion
name: Riley, Brien P.
name: Chan, Raymond C.K.
name: Wildenauer, Dieter B.
name: Oh, Sang-Yun
name: Purcell, Shaun M.
name: Cohen, Nadine
name: Stefansson, Hreinn
name: Ikeda, Masashi
name: Wendland, Jens R.
name: Mattingsdal, Morten
name: Campion, Dominique
name: Magnusson, Patrik K.E.
name: Gill, Michael
name: Albus, Margot
name: Nelis, Mari
name: Kucinskiene, Zita Ausrele
name: Crowley, James J.
name: Li, Tao
name: Breen, Gerome
name: Franke, Lude
name: Thirumalai, Srinivas
name: Weinberger, Daniel R.
name: Gejman, Pablo V.
name: Quested, Digby
name: Dikeos, Dimitris
name: Olincy, Ann
name: Nicodemus, Kristin K.
name: Keller, Matthew C.
name: Owen, Michael J.
name: Drapeau, Elodie
name: Visscher, Peter M.
name: McIntosh, Andrew M.
name: Straub, Richard E.
name: Reimers, Mark A.
name: Nertney, Deborah A.
name: Buxbaum, Joseph D.
name: Webb, Bradley T.
name: Silverman, Jeremy M.
name: Williams, Nigel M.
name: Neale, Benjamin M.
name: Hong Lee, 
name: Papadimitriou, George N.
name: Laurent, Claudine
name: Lubinski, Jan
name: Robert Cloninger, 
name: Li, Miaoxin
name: Silagadze, Teimuraz
name: Amin, Farooq
name: Kahn, René S.
name: Wong, Emily H. M.
name: Buccola, Nancy G.
name: Svrakic, Dragan M.
name: Escott-Price, Valentina
name: Wang, Qiang
name: Schall, Ulrich
name: Clair, David S.
name: Nisenbaum, Laura
name: Chee Keong, Jimmy Lee
name: Hansen, Mark
name: Malhotra, Anil K.
name: Paunio, Tiina
name: Holmans, Peter A.
name: Kim, Yunjung
name: Anthony O'Neill, 
name: Wray, Naomi R.
name: Ruderfer, Douglas M.
name: Nöthen, Markus M.
name: Steinberg, Stacy
name: Chen, Eric Y.H.
name: Macek, Milan
name: Freedman, Robert
name: Rujescu, Dan
name: Witt, Stephanie H.
name: Farrell, Martilias S.
name: Cheung, Eric F.C.
name: Mallet, Jacques
name: Ripke, Stephan
name: Essioux, Laurent
name: Müller-Myhsok, Bertram
name: Heilmann-Heimbach, Stefanie
name: Abdellaoui, Abdel
name: Müller-Mhysok, Betram
name: Mors, Ole
name: Eichhammer, Peter
name: Knight, Jo
name: Levinson, Douglas F.
name: Pantelis, Christos
name: Perkins, Diana O.
name: Roussos, Panos
name: Neale, Benjamin
name: Schulze, Thomas G.
name: Legge, Sophie E.
name: Michie, Patricia T.
name: Fanous, Ayman H.
name: Julià, Antonio
name: Friedman, Joseph I.
name: Zimprich, Fritz
name: Meier, Sandra
name: Murray, Robin M.
name: Carrera, Noa
name: Van Os, Jim
name: Freimer, Nelson B.
name: Blackwood, Douglas H. R.
name: Parkhomenko, Elena
name: Sanders, Alan R.
name: Kavanagh, David
name: Tosato, Sarah
name: Chambert, Kimberly D.
name: Black, Donald W.
name: Simonson, Matthew A.
name: Nöthen, Markus M.
name: Rasmussen, Henrik B.
name: Sullivan, Patrick F.
name: Maher, Brion S.
name: Gratten, Jacob
name: Ophoff, Roel A.
name: Lencz, Todd
name: Kirov, George
name: Joa, Inge
name: Zai, Clement C.
name: Spencer, Chris C.A.
name: Limborska, Svetlana
name: Forstner, Andreas J.
name: Godard, Stephanie
name: Hoffmann, Per
name: Shi, Jianxin
name: Khrunin, Andrey
name: Hofman, Andrea
name: Degenhardt, Franziska
name: Hultman, Christina M.
name: Nikitina-Zake, Liene
name: Salomaa, Veikko
name: Lerer, Bernard
name: Myin-Germeys, Inez
name: Walters, James T.R.
name: Petryshen, Tracey L.
name: Nestadt, Gerald
name: Rietschel, Marcella
name: Adolfsson, Rolf
name: Konte, Bettina
name: Hirschhorn, Joel N.
name: Subramaniam, Mythily
name: Wolen, Aaron R.
name: Richards, Alexander L.
name: Bulik-Sullivan, Brendan
name: Curtis, David
name: Scott Stroup, 
name: Wormley, Brandon K.
name: Pocklington, Andrew J.
name: Karjalainen, Juha
name: Melle, Ingrid
name: Jönsson, Erik G.
name: Reichenberg, Abraham
name: Kähler, Anna K.
name: Bjelland, Douglas W.
name: Domenici, Enrico
name: Huang, Hailiang
name: McDonald, Colm
name: Collier, David A.
name: Cheng, Wei
name: Bramon, Elvira
name: Posthuma, Danielle
name: Söderman, Erik
name: Alexander, Madeline
name: Bruggeman, Richard
name: Moran, Jennifer L.
name: Xi, Hualin Simon
name: Djurovic, Srdjan
name: Darvasi, Ariel
name: Sigurdsson, Engilbert
name: Hougaard, David M.
name: O’Dushlaine, Colm
name: Williams, Stephanie
name: Cichon, Sven
name: Walsh, Dermot
name: Dudbridge, Frank
name: Ehrenreich, Hannelore
name: Liu, Jianjun
name: Pato, Michele T.
name: Mokrab, Younes
name: Lee, Phil
name: Begemann, Martin
name: Iwata, Nakao
name: Kucinskas, Vaidutis
name: de Haan, Lieuwe
name: Hollegaard, Mads V.
name: Suvisaari, Jaana
name: Werge, Thomas
name: McCarroll, Steven A.
name: Howrigan, Daniel P.
name: Esko, Tõnu
name: Nordin, Annelie
name: Pimm, Jonathan
name: Golimbet, Vera
name: Corvin, Aiden
name: Hartmann, Annette M.
name: Byerley, William
name: Li, Qingqin S.
name: Johnson, Emma C.
name: Veijola, Juha
name: Craddock, Nick
name: Strengman, Eric
name: Weiser, Mark
name: Bergen, Sarah E.
name: Gurling, Hugh
name: Eriksson, Johan
name: McCarley, Robert W.
name: Schwab, Sibylle G.
name: Schubert, Christian R.
name: Pejovic-Milovancevic, Milica
name: Lieberman, Jeffrey
name: Maier, Wolfgang
name: Goldstein, Jacqueline I.
name: Bigdeli, Tim B.
name: Keller, Matthew C.
name: Pers, Tune H.
name: Marsal, Sara
name: Agerbo, Esben
name: Cantor, Rita M.
name: Melegh, Bela
name: Lönnqvist, Jouko
name: Daly, Mark J.
name: Cai, Guiqing
name: Duan, Jubao
name: Smoller, Jordan W.
name: Sklar, Pamela
name: Papiol, Sergi
name: Loughland, Carmel M.
name: Hamshere, Marian L.
name: Giegling, Ina
name: Cahn, Wiepke
name: Catts, Stanley V.
name: Zheng, Xuebin
name: Carr, Vaughan J.
name: Børglum, Anders D.
name: Roffman, Joshua L.
name: Hansen, Thomas
name: Sim, Kang
name: Belliveau, Richard A.
name: Morris, Derek W.
name: Pietiläinen, Olli
name: Metspalu, Andres
name: Durmishi, Naser
name: Karachanak-Yankova, Sena
name: Del Favero, Jurgen
name: So, Hon-Cheong
name: Klovins, Janis
name: Scolnick, Edward M.
name: Davidson, Michael
name: Henskens, Frans A.
name: Mowry, Bryan
name: Chen, Ronald Y.L.
name: Georgieva, Lyudmila
name: Szatkiewicz, Jin P.
name: McQuillin, Andrew
name: Kendler, Kenneth S.
name: O'Callaghan, Eadbhard
name: Borglum, Anders
name: Pato, Carlos N.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2016

description: 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.