Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

The Schizophrenia Psychiatric Genome-Wide Association Study Consortium, Matthew C. Keller, Matthew A. Simonson, Stephan Ripke, Ben M. Neale, Pablo V. Gejman, Daniel P. Howrigan, Sang Hong Lee, Todd Lencz, Douglas F. Levinson, Patrick F. Sullivan, David St Clair, Hong Lee, Marcella Rietschel, Markus M. Nöthen, Wolfgang Maier, Thomas G. Schulze, Manuel Mattheisen, George K. Kirov, Michael C. O’Donovan & 31 others Peter A. Holmans, Lyudmila Georgieva, Ivan Nikolov, Hywel J. Williams, Draga Toncheva, Vihra Milanova, Michael J. Owen, Nicholas Craddock, Marian Hamshere, Valentina Moskvina, Sarah Dwyer, Stan Zammit, Patrick F. Sullivan, Dan Yu Lin, Edwin van den Oord, Yunjung Kim, T. Scott Stroup, Jeffrey A. Lieberman, Thomas Hansen, Andrés Ingason, Line Olsen, Henriette Schmock, Celina Skjødt, Johan Hilge Thygesen, Anders Rosengren, Thomas Werge, Derek W. Morris, Colm T. O’Dushlaine, Elaine Kenny, Emma M. Quinn, Michael Gill

Research output: Contribution to journalArticle

66 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.

LanguageEnglish
Article numbere1002656
JournalPLoS genetics
Volume8
Issue number4
DOIs
Publication statusPublished - 1 Apr 2012

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (2012). Runs of homozygosity implicate autozygosity as a schizophrenia risk factor. PLoS genetics, 8(4), [e1002656]. https://doi.org/10.1371/journal.pgen.1002656
The Schizophrenia Psychiatric Genome-Wide Association Study Consortium. / Runs of homozygosity implicate autozygosity as a schizophrenia risk factor. In: PLoS genetics. 2012 ; Vol. 8, No. 4.
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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.",
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 Hong Lee 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’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 Sullivan, {Patrick F.} 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’Dushlaine, {Colm T.} and Elaine Kenny and Quinn, {Emma M.} and Michael Gill",
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The Schizophrenia Psychiatric Genome-Wide Association Study Consortium 2012, 'Runs of homozygosity implicate autozygosity as a schizophrenia risk factor', PLoS genetics, vol. 8, no. 4, e1002656. https://doi.org/10.1371/journal.pgen.1002656

Runs of homozygosity implicate autozygosity as a schizophrenia risk factor. / The Schizophrenia Psychiatric Genome-Wide Association Study Consortium.

In: PLoS genetics, Vol. 8, No. 4, e1002656, 01.04.2012.

Research output: Contribution to journalArticle

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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 - Lee, Hong

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 - Sullivan, Patrick F.

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

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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.

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The Schizophrenia Psychiatric Genome-Wide Association Study Consortium. Runs of homozygosity implicate autozygosity as a schizophrenia risk factor. PLoS genetics. 2012 Apr 1;8(4). e1002656. https://doi.org/10.1371/journal.pgen.1002656