ScreenDMT reveals metabolites replicably associated with sleep disorders across three human cohorts

ScreenDMT is a statistical tool that allows researchers to replicate scientific findings consistently across various independent studies, even when dealing with high-dimensional biological data. This is crucial because traditional methods often overlook the direction of an effect or lack the statistical power needed to adjust for multiple comparisons.

To overcome these limitations, ScreenDMT has been extended to evaluate directional replication across an arbitrary number of studies, provided their sample sizes become increasingly large.

After conducting extensive simulations, the researchers found that ScreenDMT effectively controls error rates, particularly the false discovery rate (FDR), even in studies with finite sample sizes. Moreover, it yields higher statistical power compared to alternative methods, especially when analyzing three studies. To test the efficacy of this approach, the scientists applied ScreenDMT to untargeted blood metabolomics profiles from three diverse human cohorts: ARIC (N=1,337), MESA (N=1,874), and HCHS/SOL (N=6,180).

The goal was to identify replicable biomarkers for various sleep disorders, including dichotomous insomnia, long sleep, short sleep, and excessive daytime sleepiness (EDS).

The analysis revealed that low levels of cortisol were consistently associated with EDS, while high levels of n-formylmethionine were linked to long sleep duration. Additionally, directional pathway analysis demonstrated that low levels of xanthine metabolites were associated with insomnia across these populations. These findings collectively validate ScreenDMT as a robust methodology for simultaneously replicating multi-cohort studies and provide valuable insights into the metabolic signatures underlying sleep disorders in diverse populations.