Perspective on Beyond Statistical Significance: Finding Meaningful Effects

Genome-wide association studies (GWASs) in psychiatry have recently identified many loci that affect a wide variety of disorders and related traits, although the number of associated loci varies widely among psychiatric and substance-use traits. The successes of GWAS have triggered thoughts about how to move beyond identification of loci (which contain a very large number of variants), to identification of the functional variants within them that actually contribute to the risk for the traits, and from there to identifying the genes, pathways, and mechanisms involved. The hope is that knowledge of the key genes and pathways will lead to better diagnosis, treatment, and prevention of these complex disorders. On September 2, 2020, three institutes within the US National Institutes of Health (NIH) sponsored a virtual meeting entitled “Beyond Statistical Significance: Finding Meaningful Effects” devoted to exploring these issues. The structure of the meeting – initial presentations followed by discussion sections on 3 sets of topics through which all willing participants cycled and a general discussion as a wrap-up – allowed for lively interaction and the presentation of many ideas. Dr. Elizabeth Hoffman opened the meeting by stating its objective was “To develop best practice recommendations for identifying, analyzing, and interpreting meaningful effects by engaging researchers from a range of disciplines in discussions of meaningful science that go beyond statistical significance.” It should not surprise anyone that one conclusion was that these questions are difficult and there are no one-size-fits-all answers. A good summary of the meeting has been posted at https://apps1.seiservices.com/meaningfuleffects/, with details of the presentations and the discussions. Some of these issues have been discussed in relation to the NIH Adolescent Brain Cognitive Development study [1] in a preprint recently posted to bioRxiv [2]. I will not recapitulate the meeting summary here, but rather provide a perspective on the key questions discussed, and potential future directions.