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; Schizophrenia Psychiatric Genome-Wide Association Study Consortium; Thomas Hansen; Andrés Ingason; Line Olsen; Henriette Schmock; Celina Skjødt; Johan Hilge Thygesen; Anders Rosengren; Thomas Mears Werge

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, Schizophrenia Psychiatric Genome-Wide Association Study Consortium, Thomas Hansen, Andrés Ingason, Line Olsen, Henriette Schmock, Celina Skjødt, Johan Hilge Thygesen, Anders Rosengren, Thomas Mears Werge

82 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
Journal	P L o S Genetics
Volume	8
Issue number	4
Pages (from-to)	e1002656
ISSN	1553-7390
DOIs	https://doi.org/10.1371/journal.pgen.1002656
Publication status	Published - 1 Apr 2012

Access to Document

10.1371/journal.pgen.1002656

Cite this

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., Schizophrenia Psychiatric Genome-Wide Association Study Consortium, Hansen, T., Ingason, A., Olsen, L., Schmock, H., Skjødt, C., Thygesen, J. H., Rosengren, A., & Werge, T. M. (2012). Runs of homozygosity implicate autozygosity as a schizophrenia risk factor. P L o S Genetics, 8(4), e1002656. https://doi.org/10.1371/journal.pgen.1002656

Keller, MC, Simonson, MA, Ripke, S, Neale, BM, Gejman, PV, Howrigan, DP, Lee, SH, Lencz, T, Levinson, DF, Sullivan, PF, Schizophrenia Psychiatric Genome-Wide Association Study Consortium, Hansen, T, Ingason, A, Olsen, L, Schmock, H, Skjødt, C, Thygesen, JH, Rosengren, A & Werge, TM 2012, 'Runs of homozygosity implicate autozygosity as a schizophrenia risk factor', P L o S Genetics, vol. 8, no. 4, pp. e1002656. https://doi.org/10.1371/journal.pgen.1002656

@article{e05dd61cf11641459d2cc644c691c3d2,

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 ~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 = "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 Thomas Werge 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 Werge, {Thomas Mears}",

year = "2012",

month = apr,

day = "1",

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

language = "English",

volume = "8",

pages = "e1002656",

journal = "P L o S 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 - 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 - Schizophrenia Psychiatric Genome-Wide Association Study Consortium

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 Mears

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.

U2 - 10.1371/journal.pgen.1002656

DO - 10.1371/journal.pgen.1002656

M3 - Journal article

C2 - 22511889

SN - 1553-7390

VL - 8

SP - e1002656

JO - P L o S Genetics

JF - P L o S Genetics

IS - 4

ER -

Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

Abstract

Access to Document

Fingerprint

Cite this