Runs of homozygosity implicate autozygosity as a schizophrenia risk factor
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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; Schizophrenia Psychiatric Genome-Wide Association Study Consortium; Hansen, Thomas; Ingason, Andrés; Olsen, Line; Schmock, Henriette; Skjødt, Celina; Thygesen, Johan Hilge; Rosengren, Anders; Werge, Thomas Mears.
I: P L o S Genetics, Bind 8, Nr. 4, 2012, s. e1002656.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
Y1 - 2012
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
VL - 8
SP - e1002656
JO - P L o S Genetics
JF - P L o S Genetics
SN - 1553-7390
IS - 4
ER -
ID: 48610434