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The Liptak-Stouffer Test for Meta-Analyses

Published:February 24, 2014DOI:https://doi.org/10.1016/j.biopsych.2013.11.033
      We are writing to address a potential statistical limitation in the meta-analyses reported by Byrd and Manuck (
      • Byrd A.L.
      • Manuck S.B.
      MAOA, childhood maltreatment, and antisocial behavior: Meta-analysis of a gene environment interaction.
      ) and 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.
      ). 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 (
      • Byrd A.L.
      • Manuck S.B.
      MAOA, childhood maltreatment, and antisocial behavior: Meta-analysis of a gene environment interaction.
      ) 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. (
      • 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.
      ) demonstrated a G × E interaction between a serotonin-transporter-linked polymorphic region variation and stressful life events in the development of depression. The latter topic had been addressed by Munafò et al. (
      • Munafò M.R.
      • Durrant C.
      • Lewis G.
      • Flint J.
      Gene x environment interactions at the serotonin transporter locus.
      ) and Risch et al. (
      • Risch N.
      • Herrell R.
      • Lehner T.
      • Liang K.Y.
      • Eaves L.
      • Hoh J.
      • et al.
      Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis.
      ) independently in 2009, but neither of them found significant results. 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.
      ) attributed this discrepancy to the different number of trials included in each meta-analysis. Munafò et al. (
      • Munafò M.R.
      • Durrant C.
      • Lewis G.
      • Flint J.
      Gene x environment interactions at the serotonin transporter locus.
      ) and Risch et al. (
      • Risch N.
      • Herrell R.
      • Lehner T.
      • Liang K.Y.
      • Eaves L.
      • Hoh J.
      • et al.
      Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis.
      ) estimated an overall effect size of a limited number of trials, whereas 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.
      ) combined the p values of a much larger group of studies. The main differences between these two types of meta-analysis are presented below.
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      References

        • Byrd A.L.
        • Manuck S.B.
        MAOA, childhood maltreatment, and antisocial behavior: Meta-analysis of a gene environment interaction.
        Biol Psychiatry. 2014; 75: 9-17
        • 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.
        Arch Gen Psychiatry. 2011; 68: 444-454
        • Munafò M.R.
        • Durrant C.
        • Lewis G.
        • Flint J.
        Gene x environment interactions at the serotonin transporter locus.
        Biol Psychiatry. 2009; 65: 211-219
        • Risch N.
        • Herrell R.
        • Lehner T.
        • Liang K.Y.
        • Eaves L.
        • Hoh J.
        • et al.
        Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis.
        JAMA. 2009; 301: 2462-2471
        • Fisher R.A.
        Statistical Methods for Research Workers.
        Oliver and Boyd, Edinburgh1932
        • Stouffer S.A.
        • Suchman E.A.
        • DeVinney L.C.
        • Star S.A.
        • Williams Jr, R.M.
        The American Soldier, Vol. 1: Adjustment During Army Life.
        Princeton University Press, Princeton, NJ1949
        • Liptak T.
        On the combination of independent tests.
        Magyar Tud Akad Mat Kutato Int Kozl. 1958; 3: 171-197
        • Borenstein M.
        • Hedges R.V.
        • Higgins J.P.T.
        • Rothstein H.R.
        Introduction to Meta-Analysis.
        Wiley Edition, West Sussex, UK2009
        • Darlington R.B.
        • Hayes A.F.
        Combining independent p values: Extensions of the Stouffer and binomial methods.
        Psychol Methods. 2000; 5: 496-515
        • Won S.
        • Morris N.
        • Lu Q.
        • Elston R.C.
        Choosing an optimal method to combine p-values.
        Stat Med. 2009; 28: 1537-1553
        • Hedges L.V.
        • Cooper H.
        • Bushman B.J.
        Testing the null hypothesis in meta-analysis: A comparison of combined probability and confidence interval procedures.
        Psychol Bull. 1992; 111: 188-194
        • Rice W.R.
        A consensus combined P-value test and the family-wide significance of component tests.
        Biometrics. 1990; 46: 303-308
        • Whitlock M.C.
        Combining probability from independent tests: The weighted Z-method is superior to Fisher’s approach.
        J Evol Biol. 2005; 18: 1368-1373

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      • Reply To: The Liptak-Stouffer Test for Meta-Analyses
        Biological PsychiatryVol. 77Issue 1
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          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 (1) and the second published elsewhere by Karg et al. (2). These focus, respectively, on two reports of gene-environment (G × E) interactions, published in 2002 and 2003 (3,4), that have spawned over 80 replication attempts.
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