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.
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado at Boulder, Boulder, Colorado, United States of America. matthew.c.keller@gmail.com
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Keller
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Simonson
authors.forename: Stephan
authors.initials: S
authors.lastname: Ripke
authors.forename: Ben M
authors.initials: BM
authors.lastname: Neale
authors.forename: Pablo V
authors.initials: PV
authors.lastname: Gejman
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Howrigan
authors.forename: Sang Hong
authors.initials: SH
authors.lastname: Lee
authors.forename: Todd
authors.initials: T
authors.lastname: Lencz
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Levinson
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
mesh_terms: D000483:Alleles; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*; D044465:White People / Q000235:genetics