Measuring shared variants in cohorts of discordant siblings with applications to autism

Kenny Ye, Ivan Iossifov, Dan Levy, Boris Yamrom, Andreas Buja, Abba M. Krieger, Michael Wigler

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


We develop a method of analysis [affected to discordant sibling pairs (A2DS)] that tests if shared variants contribute to a disorder. Using a standard measure of genetic relation, test individuals are compared with a cohort of discordant sibling pairs (CDS) to derive a comparative similarity score. We ask if a test individual is more similar to an unrelated affected than to the unrelated unaffected sibling from the CDS and then, sum over such individuals and pairs. Statistical significance is judged by randomly permuting the affected status in the CDS. In the analysis of published genotype data from the Simons Simplex Collection (SSC) and the Autism Genetic Resource Exchange (AGRE) cohorts of children with autism spectrum disorder (ASD), we find strong statistical significance that the affected are more similar to the affected than to the unaffected of the CDS (P value ∼ 0.00001). Fathers in multiplex families have marginally greater similarity (P value = 0.02) to unrelated affected individuals. These results do not depend on ethnic matching or gender.

Original languageEnglish (US)
Pages (from-to)7073-7076
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number27
StatePublished - Jul 3 2017


  • Autism
  • Discordant siblings
  • Shared variants

ASJC Scopus subject areas

  • General


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