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Promise and pitfalls in the meta-analysis of genetic association studies: a response to Sen and Schinka

Molecular Psychiatry volume 10, pages 895–897 (2005)Cite this article

SIR—The two responses1, 2 to our recent meta-analysis3 offer an opportunity to revisit our analysis and review critically the meta-analysis methodology we employed. In addition, they illustrate the growing interest in meta-analytic techniques, both as a means by which the disparate literature regarding candidate gene studies of psychiatric and behavioural phenotypes may be reconciled to some degree, and as a means by which the perennial problem of lack of statistical power in such research can be addressed.4

What is apparent from our meta-analysis and the subsequent correspondence by Sen et al1 and Schinka2 is that different approaches to statistical analysis can, in meta-analysis as well as primary research, afford somewhat different results. One issue lies in the conversion of continuous scales to standard units. Where it is not possible to convert continuous scales to standard units, the most commonly used (and preferred) approach to combining studies is to calculate standardised mean differences.5 Within this class of approaches, the most popular methods are Cohen's d, Hedges' adjusted g, or Glass's Δ.5 A recent review of definitions, assumptions and comparisons is available.5 In revisiting our analysis, we applied Cohen's d, pooling using a fixed effects model, due to a lack of significant between-study heterogeneity, and found results similar to those reported by Schinka.2 These results are presented in Table 1, and show a strong dominant effect of 5-HTT LPR on NEO neuroticism, and a more modest but nevertheless significant recessive effect on TCI/TPQ harm avoidance.

Table 1 Standardised mean differences
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Authors and Affiliations

  1. Department of Experimental Psychology, University of Bristol, Bristol, UK

    M R Munafò

  2. Cancer Research UK Centre for Statistics in Medicine, University of Oxford, Oxford, UK

    T Clark

  3. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    J Flint

Authors
  1. M R Munafò
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  2. T Clark
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  3. J Flint
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Correspondence to M R Munafò.

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Munafò, M., Clark, T. & Flint, J. Promise and pitfalls in the meta-analysis of genetic association studies: a response to Sen and Schinka. Mol Psychiatry 10, 895–897 (2005). https://doi.org/10.1038/sj.mp.4001706

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