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Commentary| Volume 76, ISSUE 8, P599-600, October 15, 2014

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Advances in the Genetics of Attention-Deficit/Hyperactivity Disorder

  • Stephen V. Faraone
    Correspondence
    Address correspondence to Stephen Faraone, Ph.D., SUNY Upstate Medical University, Department of Psychiatry and Behavioral Sciences, 750 East Adams Street, Syracuse, NY 13210
    Affiliations
    Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York.
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      One of the most replicated findings in studies of attention-deficit/hyperactivity disorder (ADHD) is its very high heritability, which averages approximately 75% across 20 twin studies conducted on three continents (
      • Faraone S.V.
      • Mick E.
      Molecular genetics of attention deficit hyperactivity disorder.
      ). ADHD’s high heritability kick-started a search for DNA variants with the hope that their discovery would lead to advances in diagnosis and treatment. During the dark decades of linkage and candidate gene studies, progress was slow, but in the past few years, boosted by genome-wide association studies (GWAS), the ADHD research community has made real breakthroughs. GWAS taught us that 25% to 30% of ADHD’s heritability could be accounted for by a polygenic liability consisting of many common DNA variants (
      • Lee S.H.
      • Ripke S.
      • Neale B.M.
      • Faraone S.V.
      • Purcell S.M.
      • Perlis R.H.
      • et al.
      Cross-Disorder Group of the Psychiatric Genomics Consortium
      Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.
      ). GWAS also gave us replicated discoveries of rare deletions and insertions known as copy number variants (CNVs) (
      • Williams N.M.
      • Franke B.
      • Mick E.
      • Anney R.J.
      • Freitag C.M.
      • Gill M.
      • et al.
      Genome-wide analysis of copy number variants in attention deficit/hyperactivity disorder confirms the role of rare variants and implicates duplications at 15q13.3.
      ). These GWAS data confirmed what many had suspected from epidemiologic data, that ADHD’s genetic liability consists of a complex mixture of common and rare DNA variants.
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