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Common or Rare Variants for Complex Traits?

  • Marcus R. Munafò
    Correspondence
    Address correspondence to Marcus R. Munafò, Ph.D., University of Bristol, School of Experimental Psychology, 12a Priory Road, Bristol BS8 1TU, United Kingdom
    Affiliations
    Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol

    United Kingdom Centre for Tobacco and Alcohol Studies and School of Experimental Psychology, University of Bristol, Bristol
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  • Jonathan Flint
    Affiliations
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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      Vrieze et al. (
      • Vrieze S.I.
      • Feng S.
      • Miller M.B.
      • Hicks B.M.
      • Pankratz N.
      • Abecasis G.R.
      • et al.
      Rare nonsynonymous exonic variants in addiction and behavioral disinhibition.
      ) report a failure to identify any rare genetic variants associated with addiction-related phenotypes, using a rare variant genotyping chip in a sample of over 7000 individuals nested within over 2000 pedigrees. While sequencing costs remain high, the use of rare variant chips may be a cost-effective approach, given the large samples that will be required to identify these variants. However, it is worth considering what we can expect to learn from these efforts and what we have already learned.
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      Linked Article

      • Rare Nonsynonymous Exonic Variants in Addiction and Behavioral Disinhibition
        Biological PsychiatryVol. 75Issue 10
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          Substance use is heritable, but few common genetic variants have been associated with these behaviors. Rare nonsynonymous exonic variants can now be efficiently genotyped, allowing exome-wide association tests. We identified and tested 111,592 nonsynonymous exonic variants for association with behavioral disinhibition and the use/misuse of nicotine, alcohol, and illicit drugs.
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