Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

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; George Kirov; Michael Conlon O'Donovan; Peter Alan Holmans; Lyudmila Georgieva; Ivan Nikolov; Hywel John Williams; Michael John Owen; Nicholas John Craddock; Marian Lindsay Hamshere; Valentina Escott-Price; Sarah Lynne Dwyer; Stanley Zammit

doi:10.1371/journal.pgen.1002656

Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

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, George Kirov, Michael Conlon O'Donovan, Peter Alan Holmans, Lyudmila Georgieva, Ivan Nikolov, Hywel John Williams, Michael John Owen, Nicholas John Craddock, Marian Lindsay Hamshere, Valentina Escott-PriceSarah Lynne Dwyer, Stanley Zammit

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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 ar12617% 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
Number of pages	11
Journal	PLoS Genetics
Volume	8
Issue number	4
DOIs	https://doi.org/10.1371/journal.pgen.1002656
Publication status	Published - 1 Apr 2012

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Keller, M. C., Simonson, M. A., Ripke, S., Neale, B. M., Gejman, P. V., Howrigan, D. P., Lee, S. H., Lencz, T., Levinson, D. F., Sullivan, P. F., Kirov, G., O'Donovan, M. C., Holmans, P. A., Georgieva, L., Nikolov, I., Williams, H. J., Owen, M. J., Craddock, N. J., Hamshere, M. L., ... Zammit, S. (2012). Runs of homozygosity implicate autozygosity as a schizophrenia risk factor. PLoS Genetics, 8(4). https://doi.org/10.1371/journal.pgen.1002656

@article{64eeb9ff00f24b93a8eaf3993992d861,

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 ar12617% 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 = "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 George Kirov and O'Donovan, {Michael Conlon} and Holmans, {Peter Alan} and Lyudmila Georgieva and Ivan Nikolov and Williams, {Hywel John} and Owen, {Michael John} and Craddock, {Nicholas John} and Hamshere, {Marian Lindsay} and Valentina Escott-Price and Dwyer, {Sarah Lynne} and Stanley Zammit",

year = "2012",

month = apr,

day = "1",

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

language = "English",

volume = "8",

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issn = "1553-7390",

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Keller, MC, Simonson, MA, Ripke, S, Neale, BM, Gejman, PV, Howrigan, DP, Lee, SH, Lencz, T, Levinson, DF, Sullivan, PF, Kirov, G, O'Donovan, MC, Holmans, PA, Georgieva, L, Nikolov, I, Williams, HJ, Owen, MJ, Craddock, NJ, Hamshere, ML, Escott-Price, V, Dwyer, SL & Zammit, S 2012, 'Runs of homozygosity implicate autozygosity as a schizophrenia risk factor', PLoS Genetics, vol. 8, no. 4. https://doi.org/10.1371/journal.pgen.1002656

TY - JOUR

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

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 - Kirov, George

AU - O'Donovan, Michael Conlon

AU - Holmans, Peter Alan

AU - Georgieva, Lyudmila

AU - Nikolov, Ivan

AU - Williams, Hywel John

AU - Owen, Michael John

AU - Craddock, Nicholas John

AU - Hamshere, Marian Lindsay

AU - Escott-Price, Valentina

AU - Dwyer, Sarah Lynne

AU - Zammit, Stanley

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 ar12617% 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 ar12617% 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.

U2 - 10.1371/journal.pgen.1002656

DO - 10.1371/journal.pgen.1002656

M3 - Article (Academic Journal)

C2 - 22511889

SN - 1553-7390

VL - 8

JO - PLoS Genetics

JF - PLoS Genetics

IS - 4

ER -

Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

Abstract

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