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.