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DSM-5 and Psychiatric Genetics — Round Hole, Meet Square Peg

  • Joseph D. Buxbaum
    Correspondence
    Address correspondence to Joseph D. Buxbaum, Ph.D., Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1668, New York, NY 10029
    Affiliations
    Seaver Autism Center for Research and Treatment, Departments of Psychiatry, Neuroscience, and Genetics and Genomic Sciences, Friedman Brain Institute and Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
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Published:February 28, 2015DOI:https://doi.org/10.1016/j.biopsych.2015.02.031
      It is useful to consider genetic variation as either common (e.g., an allele found in >5% of the population) or rare because these categories of variation are analyzed using different approaches and have different properties. Most importantly, for neurodevelopmental disorders (NDDs), common genetic variation (e.g., single nucleotide polymorphism [SNP]) is associated with very small effect sizes given evolution constraints on deleterious variation (negative or purifying selection), whereas rare variation can be associated with a much wider range of effect sizes. Chaste et al. (
      • Chaste P.
      • Klei L.
      • Sanders S.J.
      • Hus V.
      • Murtha M.T.
      • Lowe J.K.
      • et al.
      A genomewide association study of autism using the Simons Simplex Collection: Does reducing phenotypic heterogeneity in autism increase genetic homogeneity?.
      ) look at common variation in autism spectrum disorder (ASD) to answer questions about relationships between clinical and genetic heterogeneity.
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