Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

Keller, Matthew C., Simonson, Matthew A., Ripke, Stephan, Neale, Ben M., Gejman, Pablo V., Howrigan, Daniel P., Lee, Sang Hong, Lencz, Todd, Levinson, Douglas F., Sullivan, Patrick F., Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Georgieva, Lyudmila, Nikolov, Ivan, Williams, Hywel John ORCID: https://orcid.org/0000-0001-7758-0312, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610, Hamshere, Marian Lindsay ORCID: https://orcid.org/0000-0002-8990-0958, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Dwyer, Sarah Lynne and Zammit, Stanley ORCID: https://orcid.org/0000-0002-2647-9211 2012. Runs of homozygosity implicate autozygosity as a schizophrenia risk factor. Plos Genetics 8 (4) , e1002656. 10.1371/journal.pgen.1002656

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Systems Immunity Research Institute (SIURI) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Public Library of Science
ISSN:	1553-7390
Date of First Compliant Deposit:	30 March 2016
Last Modified:	11 Oct 2023 21:49
URI:	https://orca.cardiff.ac.uk/id/eprint/43108

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