Figure 2

Bias (%) in the between-study variance (τ² ) estimate (statistical heterogeneity) for the bi-allelic case for a representative scenario of a variant with modest effect (OR = 1.3) following distinct modes of action (A-B, dominant; C-D, multiplicative, E-F, over-dominant) under moderate heterogeneity (τ² = 0.025). The sample size for each study was randomly sampled from a uniform distribution on the interval [500-1000] and split equally into cases and controls (i.e. case to control ratio = 1). Color lines depict bias estimates under different models of analysis: green (dominant), blue (per-allele odds ratio), red (recessive) and black (generalized odds ratio). Results for the log-additive trend model of analysis were omitted because the striking similarity with the results of the per-allele odds ratio. Scenarios with a genuine variant acting recessively are not displayed for simplicity, since all models of analysis (except the recessive) are unable to capture the underlying τ² even when the frequency of risk alleles is high. Scenarios with alternative magnitudes of heterogeneity yielded qualitatively identical results. Results are based on the median value from 5,000 replications. f, allelic frequency.