Replicable brain–phenotype associations require large-scale neuroimaging data

Numerous neuroimaging studies have investigated the neural basis of interindividual differences but the replicability of brain–phenotype associations remains largely unknown. We used the UK Biobank neuroimaging dataset (N = 37,447) to examine associations with six variables related to physical and mental health: age, body mass index, intelligence, memory, neuroticism and alcohol consumption, and assessed the improvement of replicability for brain–phenotype associations with increasing sampling sizes. Age may require only 300 individuals to provide highly replicable associations but other phenotypes required 1,500 to 3,900 individuals. The required sample size showed a negative power law relation with the estimated effect size. When only comparing the upper and lower quarters, the minimally required sample sizes for imaging decreased by 15–75%. Our findings demonstrate that large-scale neuroimaging data are required for replicable brain–phenotype associations, that this can be mitigated by preselection of individuals and that small-scale studies may have reported false positive findings.