This press release about this article considers gene by environment (childhood abuse) interactions contributing to the risk of depression. The authors analysed a sample of 2679 Spanish primary care patients ages 18 to 75. The paper reports that those who have low functioning alleles in functional genes for neurotrophism (BDNF) and serotonin transmission are particularly vulnerable to the effects of childhood abuse (psychological, physical or sexual) as a risk factor for clinical depression. They also included an additional level of interaction with treatment, taking into account the response to antidepressants.
I am sceptical about the statistical power necessary for testing 3-way interactions among 2679 subjects, not to mention the use of odds ratios for common outcomes. But my biggest gripe is that they tested for synergism by looking at the p-value for the product interaction term in a logistic regression model, which detects deviation from multiplicativity. Deviation from additivity is really what they want here. In fact, their estimates are mostly greater than multiplicative, and therefore there is no doubt about them being synergistic. But it presents an incorrect method for making this G x E interaction analysis. Not to mention that they exponentiate the interaction term coefficient and call that an odds ratio. It would be better of course to use a measure like RERI to detect greater than additive joint effects between genotype and abuse history, but since the outcome is not rare, it is also better to rely on the RR rather than the OR in making that calculation, as noted by Kalilani and Atashili 2006.
I am sceptical about the statistical power necessary for testing 3-way interactions among 2679 subjects, not to mention the use of odds ratios for common outcomes. But my biggest gripe is that they tested for synergism by looking at the p-value for the product interaction term in a logistic regression model, which detects deviation from multiplicativity. Deviation from additivity is really what they want here. In fact, their estimates are mostly greater than multiplicative, and therefore there is no doubt about them being synergistic. But it presents an incorrect method for making this G x E interaction analysis. Not to mention that they exponentiate the interaction term coefficient and call that an odds ratio. It would be better of course to use a measure like RERI to detect greater than additive joint effects between genotype and abuse history, but since the outcome is not rare, it is also better to rely on the RR rather than the OR in making that calculation, as noted by Kalilani and Atashili 2006.
RSS Feed