On optimal two‐stage testing of multiple mediators

Djordjilović, Vera; Hemerik, Jesse; Thoresen, Magne

doi:10.1002/bimj.202100190

Cited by 7 publications

(1 citation statement)

References 31 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We assessed the performance of methods that provide adjusted p-values by simulating two studies with the same 1,000 features or analytes following the simulations in (22). We simulated normally distributed statistics with variance of one per analyte per study.…”

Section: Replication Simulationsmentioning

confidence: 99%

ScreenDMT reveals linoleic acid diols replicably associate with BMI and stimulate adipocyte calcium fluxes

Dreyfuss

Djordjilović

Hui

et al. 2023

Preprint

View full text Add to dashboard Cite

Activating brown adipose tissue (BAT) improves systemic metabolism, making it a promising target for metabolic syndrome. An activator of BAT is 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), which we previously identified to be inversely associated with body mass index (BMI) and which directly improves metabolism in other tissues. Here we profile plasma lipidomics from a cohort of 83 people and test which lipids' association with BMI replicates in a concordant direction using our novel tool ScreenDMT, whose power and validity we demonstrate via mathematical proofs and simulations. We find that the linoleic acid diols 12,13-diHOME and 9,10-diHOME both replicably inversely associate with BMI and mechanistically activate calcium fluxes in mouse brown and white adipocytes in vitro. ScreenDMT can be applied to test directional replication, directional mediation, and qualitative interactions, and our results identify 9,10-diHOME and the pathway stimulated by linoleic acid diols as candidate therapeutic targets to improve systemic metabolism.

show abstract

Section: Replication Simulationsmentioning

confidence: 99%

ScreenDMT reveals linoleic acid diols replicably associate with BMI and stimulate adipocyte calcium fluxes

Dreyfuss

Djordjilović

Hui

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

On optimal two‐stage testing of multiple mediators

Djordjilović

Hemerik²,

Thoresen

2022

Biometrical J

View full text Add to dashboard Cite

Mediation analysis in high‐dimensional settings often involves identifying potential mediators among a large number of measured variables. For this purpose, a two‐step familywise error rate procedure called ScreenMin has been recently proposed. In ScreenMin, variables are first screened and only those that pass the screening are tested. The proposed data‐independent threshold for selection has been shown to guarantee asymptotic familywise error rate. In this work, we investigate the impact of the threshold on the finite‐sample familywise error rate. We derive a power maximizing threshold and show that it is well approximated by an adaptive threshold of Wang et al. (2016, arXiv preprint arXiv:1610.03330). We illustrate the investigated procedures on a case‐control study examining the effect of fish intake on the risk of colorectal adenoma. We also apply our procedure in the context of replicability analysis to identify single nucleotide polymorphisms (SNP) associated with crop yield in two distinct environments.

show abstract

ScreenDMT reveals DiHOMEs are replicably inversely associated with BMI and stimulate adipocyte calcium influx

Dreyfuss,

Djordjilović,

Pan

et al. 2024

Commun Biol

View full text Add to dashboard Cite

Activating brown adipose tissue (BAT) improves systemic metabolism, making it a promising target for metabolic syndrome. BAT is activated by 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), which we previously identified to be inversely associated with BMI and which directly improves metabolism in multiple tissues. Here we profile plasma lipidomics from 83 people and test which lipids’ association with BMI replicates in a concordant direction using our novel tool ScreenDMT, whose power and validity we demonstrate via mathematical proofs and simulations. We find that the linoleic acid diols 12,13-diHOME and 9,10-diHOME are both replicably inversely associated with BMI and mechanistically activate calcium influx in mouse brown and white adipocytes in vitro, which implicates this signaling pathway and 9,10-diHOME as candidate therapeutic targets. ScreenDMT can be applied to test directional mediation, directional replication, and qualitative interactions, such as identifying biomarkers whose association is shared (replication) or opposite (qualitative interaction) across diverse populations.

show abstract

On optimal two‐stage testing of multiple mediators

Cited by 7 publications

References 31 publications

ScreenDMT reveals linoleic acid diols replicably associate with BMI and stimulate adipocyte calcium fluxes

ScreenDMT reveals linoleic acid diols replicably associate with BMI and stimulate adipocyte calcium fluxes

On optimal two‐stage testing of multiple mediators

ScreenDMT reveals DiHOMEs are replicably inversely associated with BMI and stimulate adipocyte calcium influx

Contact Info

Product

Resources

About