Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

The Schizophrenia Psychiatric Genome-Wide Association Study Consortium

doi:10.1371/journal.pgen.1002656

Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

The Schizophrenia Psychiatric Genome-Wide Association Study Consortium

University of Colorado Boulder
Massachusetts General Hospital
Broad Institute
NorthShore University HealthSystem
University of Chicago
QIMR Berghofer Medical Research Institute
Northwell Health System
Laboratory of Developmental Erythropoiesis
Albert Einstein College of Medicine
Stanford University
Karolinska Institutet
University of North Carolina
University of North Carolina at Chapel Hill
University of North Carolina
University of Aberdeen
University of Bonn
ICS-6/Structural Biochemistry
Heidelberg University
National Institute of Mental Health Intramural Research Program
Cardiff University
“Alexandrovska” University Hospital
Virginia Commonwealth University
Columbia University
Copenhagen University Hospital
University Hospital
Trinity College Dublin
University of Edinburgh
University of Strathclyde
National Cancer Institute (NCI)
Louisiana State University
University of Queensland
University of Colorado Anschutz Medical Campus
Emory University
Atlanta Department of Veterans Affairs Medical Center
University of Iowa
Icahn School of Medicine at Mount Sinai
James J. Peters VA Medical Center
University of California San Francisco
Northern California Institute for Research and Education
Washington University in St. Louis
Ludwig-Maximilians-University Munich
University of Toronto
NeuroSearch A/S
University of Southern California
Georgetown University School of Medicine
University of Oslo
Oslo University Hospital
Sørlandet Hospital
Diakonhjemmet Hospital
University Medical Centre Utrecht
University of California, Los Angeles
University of Amsterdam
Maastricht University
University of Groningen
Academic Medical Center
University College London
West Berkshire NHS Trust
University of Oxford
The Zucker Hillside Hospital

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

102 Citations (Scopus)

Abstract

Autozygosity occurs when two chromosomal segments that are identical from a common ancestor are inherited from each parent. This occurs at high rates in the offspring of mates who are closely related (inbreeding), but also occurs at lower levels among the offspring of distantly related mates. Here, we use runs of homozygosity in genome-wide SNP data to estimate the proportion of the autosome that exists in autozygous tracts in 9,388 cases with schizophrenia and 12,456 controls. We estimate that the odds of schizophrenia increase by ~17% for every 1% increase in genome-wide autozygosity. This association is not due to one or a few regions, but results from many autozygous segments spread throughout the genome, and is consistent with a role for multiple recessive or partially recessive alleles in the etiology of schizophrenia. Such a bias towards recessivity suggests that alleles that increase the risk of schizophrenia have been selected against over evolutionary time.

Original language	English
Article number	e1002656
Journal	PLoS Genetics
Volume	8
Issue number	4
DOIs	https://doi.org/10.1371/journal.pgen.1002656
Publication status	Published - 1 Apr 2012
Externally published	Yes

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10.1371/journal.pgen.1002656

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@article{d18a3c47624f41758bfd2d55b13e3852,

title = "Runs of homozygosity implicate autozygosity as a schizophrenia risk factor",

abstract = "Autozygosity occurs when two chromosomal segments that are identical from a common ancestor are inherited from each parent. This occurs at high rates in the offspring of mates who are closely related (inbreeding), but also occurs at lower levels among the offspring of distantly related mates. Here, we use runs of homozygosity in genome-wide SNP data to estimate the proportion of the autosome that exists in autozygous tracts in 9,388 cases with schizophrenia and 12,456 controls. We estimate that the odds of schizophrenia increase by \textasciitilde{}17\% for every 1\% increase in genome-wide autozygosity. This association is not due to one or a few regions, but results from many autozygous segments spread throughout the genome, and is consistent with a role for multiple recessive or partially recessive alleles in the etiology of schizophrenia. Such a bias towards recessivity suggests that alleles that increase the risk of schizophrenia have been selected against over evolutionary time.",

author = "\{The Schizophrenia Psychiatric Genome-Wide Association Study Consortium\} and Keller, \{Matthew C.\} and Simonson, \{Matthew A.\} and Stephan Ripke and Neale, \{Ben M.\} and Gejman, \{Pablo V.\} and Howrigan, \{Daniel P.\} and Lee, \{Sang Hong\} and Todd Lencz and Levinson, \{Douglas F.\} and Sullivan, \{Patrick F.\} and \{St Clair\}, David and Sven Cichon and Marcella Rietschel and N{\"o}then, \{Markus M.\} and Wolfgang Maier and Schulze, \{Thomas G.\} and Manuel Mattheisen and Kirov, \{George K.\} and O{\textquoteright}Donovan, \{Michael C.\} and Holmans, \{Peter A.\} and Lyudmila Georgieva and Ivan Nikolov and Williams, \{Hywel J.\} and Draga Toncheva and Vihra Milanova and Owen, \{Michael J.\} and Nicholas Craddock and Marian Hamshere and Valentina Moskvina and Sarah Dwyer and Stan Zammit and Lin, \{Dan Yu\} and \{van den Oord\}, Edwin and Yunjung Kim and \{Scott Stroup\}, T. and Lieberman, \{Jeffrey A.\} and Thomas Hansen and Andr{\'e}s Ingason and Line Olsen and Henriette Schmock and Celina Skj{\o}dt and Thygesen, \{Johan Hilge\} and Anders Rosengren and Thomas Werge and Morris, \{Derek W.\} and O{\textquoteright}Dushlaine, \{Colm T.\} and Elaine Kenny and Quinn, \{Emma M.\} and Michael Gill and Aiden Corvin and Blackwood, \{Douglas H.R.\} and McGhee, \{Kevin A.\} and Ben Pickard and Pat Malloy and Maclean, \{Alan W.\} and Andrew McIntosh and Gejman, \{Pablo V.\} and Sanders, \{Alan R.\} and Jubao Duan and Levinson, \{Douglas F.\} and Jianxin Shi and Buccola, \{Nancy G.\} and Mowry, \{Bryan J.\} and Robert Freedman and Farooq Amin and Black, \{Donald W.\} and Silverman, \{Jeremy M.\} and Byerley, \{William F.\} and \{Robert Cloninger\}, C. and Ina Giegling and Hartmann, \{Annette M.\} and Heike Konnerth and Marion Friedl and Bettina Konte and Pierandrea Muglia and Dan Rujescu and Pato, \{Michele T.\} and Pato, \{Carlos N.\} and Ayman Fanous and Hultman, \{Christina M.\} and Paul Lichtenstein and Bergen, \{Sarah E.\} and Shaun Purcell and Edward Scolnick and Pamela Sklar and Srdjan Djurovic and Morten Mattingsdal and Ingrid Agartz and Ingrid Melle and Andreassen, \{Ole A.\} and Ophoff, \{Roel A.\} and Cantor, \{Rita M.\} and Freimer, \{Nelson B.\} and Kahn, \{Ren{\'e} S.\} and Linszen, \{Don H.\} and \{van Os\}, Jim and Durk Wiersma and Richard Bruggeman and Wiepke Cahn and \{de Haan\}, Lieuwe",

year = "2012",

month = apr,

day = "1",

doi = "10.1371/journal.pgen.1002656",

language = "English",

volume = "8",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "4",

}

TY - JOUR

T1 - Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

AU - The Schizophrenia Psychiatric Genome-Wide Association Study Consortium

AU - Keller, Matthew C.

AU - Simonson, Matthew A.

AU - Ripke, Stephan

AU - Neale, Ben M.

AU - Gejman, Pablo V.

AU - Howrigan, Daniel P.

AU - Lee, Sang Hong

AU - Lencz, Todd

AU - Levinson, Douglas F.

AU - Sullivan, Patrick F.

AU - St Clair, David

AU - Cichon, Sven

AU - Rietschel, Marcella

AU - Nöthen, Markus M.

AU - Maier, Wolfgang

AU - Schulze, Thomas G.

AU - Mattheisen, Manuel

AU - Kirov, George K.

AU - O’Donovan, Michael C.

AU - Holmans, Peter A.

AU - Georgieva, Lyudmila

AU - Nikolov, Ivan

AU - Williams, Hywel J.

AU - Toncheva, Draga

AU - Milanova, Vihra

AU - Owen, Michael J.

AU - Craddock, Nicholas

AU - Hamshere, Marian

AU - Moskvina, Valentina

AU - Dwyer, Sarah

AU - Zammit, Stan

AU - Lin, Dan Yu

AU - van den Oord, Edwin

AU - Kim, Yunjung

AU - Scott Stroup, T.

AU - Lieberman, Jeffrey A.

AU - Hansen, Thomas

AU - Ingason, Andrés

AU - Olsen, Line

AU - Schmock, Henriette

AU - Skjødt, Celina

AU - Thygesen, Johan Hilge

AU - Rosengren, Anders

AU - Werge, Thomas

AU - Morris, Derek W.

AU - O’Dushlaine, Colm T.

AU - Kenny, Elaine

AU - Quinn, Emma M.

AU - Gill, Michael

AU - Corvin, Aiden

AU - Blackwood, Douglas H.R.

AU - McGhee, Kevin A.

AU - Pickard, Ben

AU - Malloy, Pat

AU - Maclean, Alan W.

AU - McIntosh, Andrew

AU - Gejman, Pablo V.

AU - Sanders, Alan R.

AU - Duan, Jubao

AU - Levinson, Douglas F.

AU - Shi, Jianxin

AU - Buccola, Nancy G.

AU - Mowry, Bryan J.

AU - Freedman, Robert

AU - Amin, Farooq

AU - Black, Donald W.

AU - Silverman, Jeremy M.

AU - Byerley, William F.

AU - Robert Cloninger, C.

AU - Giegling, Ina

AU - Hartmann, Annette M.

AU - Konnerth, Heike

AU - Friedl, Marion

AU - Konte, Bettina

AU - Muglia, Pierandrea

AU - Rujescu, Dan

AU - Pato, Michele T.

AU - Pato, Carlos N.

AU - Fanous, Ayman

AU - Hultman, Christina M.

AU - Lichtenstein, Paul

AU - Bergen, Sarah E.

AU - Purcell, Shaun

AU - Scolnick, Edward

AU - Sklar, Pamela

AU - Djurovic, Srdjan

AU - Mattingsdal, Morten

AU - Agartz, Ingrid

AU - Melle, Ingrid

AU - Andreassen, Ole A.

AU - Ophoff, Roel A.

AU - Cantor, Rita M.

AU - Freimer, Nelson B.

AU - Kahn, René S.

AU - Linszen, Don H.

AU - van Os, Jim

AU - Wiersma, Durk

AU - Bruggeman, Richard

AU - Cahn, Wiepke

AU - de Haan, Lieuwe

PY - 2012/4/1

Y1 - 2012/4/1

N2 - Autozygosity occurs when two chromosomal segments that are identical from a common ancestor are inherited from each parent. This occurs at high rates in the offspring of mates who are closely related (inbreeding), but also occurs at lower levels among the offspring of distantly related mates. Here, we use runs of homozygosity in genome-wide SNP data to estimate the proportion of the autosome that exists in autozygous tracts in 9,388 cases with schizophrenia and 12,456 controls. We estimate that the odds of schizophrenia increase by ~17% for every 1% increase in genome-wide autozygosity. This association is not due to one or a few regions, but results from many autozygous segments spread throughout the genome, and is consistent with a role for multiple recessive or partially recessive alleles in the etiology of schizophrenia. Such a bias towards recessivity suggests that alleles that increase the risk of schizophrenia have been selected against over evolutionary time.

AB - Autozygosity occurs when two chromosomal segments that are identical from a common ancestor are inherited from each parent. This occurs at high rates in the offspring of mates who are closely related (inbreeding), but also occurs at lower levels among the offspring of distantly related mates. Here, we use runs of homozygosity in genome-wide SNP data to estimate the proportion of the autosome that exists in autozygous tracts in 9,388 cases with schizophrenia and 12,456 controls. We estimate that the odds of schizophrenia increase by ~17% for every 1% increase in genome-wide autozygosity. This association is not due to one or a few regions, but results from many autozygous segments spread throughout the genome, and is consistent with a role for multiple recessive or partially recessive alleles in the etiology of schizophrenia. Such a bias towards recessivity suggests that alleles that increase the risk of schizophrenia have been selected against over evolutionary time.

UR - https://www.scopus.com/pages/publications/84860559560

U2 - 10.1371/journal.pgen.1002656

DO - 10.1371/journal.pgen.1002656

M3 - Article

C2 - 22511889

AN - SCOPUS:84860559560

SN - 1553-7390

VL - 8

JO - PLoS Genetics

JF - PLoS Genetics

IS - 4

M1 - e1002656

ER -

Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

Abstract

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