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Table 2 Framework for stepwise assessment of the evidence relating to gene × diet interactions

From: Proposed guidelines to evaluate scientific validity and evidence for genotype-based dietary advice

Scientific validity assessment criteria  
Study quality rating (A, B, C, D):
 * Interventional or observational design
 * Prospective and retrospective approach
 * Randomised, placebo controlled and blinded
 * Study power (high subject number with ‘effect’ allele)
 * Effect magnitude
 * P values, false discover rate (FDR) and multiple testing
 * Replication study in different populations and meta-analysis
Type of gene × diet Interaction:
 * Direct phenotype
 * Intermediate phenotype
 * Indirect phenotype
Nature of the genetic variant
 * Causal
 * In LD with functional variant
 * Associated but unknown function
Biological plausibility
 * Rated as high/medium/low/unknown
Scientific validity score for gene × diet interaction
 * Convincing
 * Probable
 * Possible
 * Not demonstrated
  1. *P values must be at least .05 to be significant. The P value must remain within .05 after correcting for multiple testing, e.g. Bonferroni
  2. aThe ‘effect magnitude’ required depends on the type of study. For example, the effect of folate on high homocysteine in carriers of the effect allele in MTHFR should be a return to normal within a few weeks of starting the intervention. The magnitude of reduction of blood pressure would be acceptable for as little as 1 mmHg, and any risk reduction, however small, for cardiovascular disease would be adequate