{"doi":"10.1101/2020.08.21.257758","title":"Towards Reproducible Brain-Wide Association Studies","abstract":"Abstract Magnetic resonance imaging (MRI) continues to drive many important neuroscientific advances. However, progress in uncovering reproducible associations between individual differences in brain structure/function and behavioral phenotypes (e.g., cognition, mental health) may have been undermined by typical neuroimaging sample sizes (median N=25) 1,2 . Leveraging the Adolescent Brain Cognitive Development (ABCD) Study 3 (N=11,878), we estimated the effect sizes and reproducibility of these brain-wide associations studies (BWAS) as a function of sample size. The very largest, replicable brain-wide associations for univariate and multivariate methods were r=0.14 and r=0.34, respectively. In smaller samples, typical for brain-wide association studies (BWAS), irreproducible, inflated effect sizes were ubiquitous, no matter the method (univariate, multivariate). Until sample sizes started to approach consortium-levels, BWAS were underpowered and statistical errors assured. Multiple factors contribute to replication failures 4–6 ; here, we show that the pairing of small brain-behavioral phenotype effect sizes with sampling variability is a key element in wide-spread BWAS replication failure. Brain-behavioral phenotype associations stabilize and become more reproducible with sample sizes of N⪆2,000. While investigator-initiated brain-behavior research continues to generate hypotheses and propel innovation, large consortia are needed to usher in a new era of reproducible human brain-wide association studies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":118226,"datarank":0.8083607594724752,"base_score":5.389071729816501,"endowment":5.389071729816501,"self_citation_contribution":0.8083607594724752,"citation_network_contribution":0.0,"self_endowment_contribution":0.8083607594724752,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":218,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.55,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":275733,"name":"Brenden Tervo‐Clemmens","orcid":"0000-0002-9557-1126","position":1,"is_corresponding":false},{"id":275731,"name":"Finnegan J. 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