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Reply To: The Liptak-Stouffer Test for Meta-Analyses

Published:February 24, 2014DOI:https://doi.org/10.1016/j.biopsych.2014.02.009
      Science is a cumulative enterprise. As more studies accumulate, it is important to integrate them, and meta-analysis is one approach to doing so. But what is the best way to conduct a meta-analysis? The commentary by Laoutidis and Luckhaus suggests limitations of two recent meta-analyses, one reported in this journal by Byrd and Manuck (
      • Byrd A.L.
      • Manuck S.B.
      MAOA, childhood maltreatment, and antisocial behavior: Meta-analysis of a gene-environment interaction.
      ) and the second published elsewhere by Karg et al. (
      • Karg K.
      • Burmeister M.
      • Shedden K.
      • Sen S.
      The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation.
      ). These focus, respectively, on two reports of gene-environment (G × E) interactions, published in 2002 and 2003 (
      • Caspi A.
      • McClay J.
      • Moffitt T.E.
      • Mill J.
      • Martin J.
      • Craig I.W.
      • et al.
      Role of genotype in the cycle of violence in maltreated children.
      ,
      • Caspi A.
      • Sugden K.
      • Moffitt T.E.
      • Taylor A.
      • Craig I.W.
      • Harrington H.
      • et al.
      Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene.
      ), that have spawned over 80 replication attempts. The earlier of the two meta-analyses targeted the interaction of life stress and polymorphic variation in the serotonin transporter gene on risk for depression, and the second meta-analysis targeted the interaction of early maltreatment and analogous variation in monoamine oxidase A (MAOA) on later antisocial behaviors. Laoutidis and Luckhaus critique our use of the Liptak-Stouffer weighted Z-test (LST) for meta-analysis, as opposed to alternative methods involving aggregated effect sizes, and suggest any conclusions permitted by the LST are limited. Here, we show why use of the LST is appropriate, and authors from our two groups have joined in this reply.
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      • The Liptak-Stouffer Test for Meta-Analyses
        Biological PsychiatryVol. 77Issue 1
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          We are writing to address a potential statistical limitation in the meta-analyses reported by Byrd and Manuck (1) and by Karg et al. (2). Both meta-analyses followed the same statistical method and investigated the role of gene-environment (G × E) interactions in the development of psychopathology. Byrd and Manuck (1) showed that there is a G × E interaction between the variable number tandem repeat polymorphism of the monoamine oxidase A promoter and childhood maltreatment in the development of antisocial behavior, while Karg et al.
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