Published April 12, 2012 | Version v1
Journal article Open

Runs of Homozygosity Implicate Autozygosity as a Schizophrenia Risk Factor

  • 1. University of Colorado
  • 2. University of Colorado at Boulder
  • 3. Massachusetts General Hospital
  • 4. University of Chicago
  • 5. Queensland Institute of Medical Research
  • 6. Northwell Health
  • 7. Stanford University
  • 8. University of North Carolina at Chapel Hill

Description

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.

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Additional details

Identifiers

DOI
10.1371/journal.pgen.1002656
Other
oai:uchicago.tind.io:10474

Funding

National Institute of Mental Health
MH085812
National Institute of Mental Health
MH61675
National Institute of Mental Health
MH085520

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Psychiatry and Behavioral Neuroscience