Why not 100 exposures? Is such a large number of exposures even useful?
"... The study identified 76 exposures significantly linked with ADRD and 34 linked with Alzheimer’s disease specifically. ..."
From the abstract:
"INTRODUCTION
Environmental exposures contribute substantially to Alzheimer's disease and related dementias (ADRD), yet comprehensive exposome-wide investigations systematically evaluating multi-domain environmental factors remain limited and lacking utility for precision medicine.
METHODS
We conducted an exposome-wide association study (ExWAS) among 499,992 UK Biobank participants, examining 193 exposures across five domains (social, physical, chemical, lifestyle, and ecosystems).
Cox proportional hazard models with Bonferroni correction identified ADRD-associated exposures. We used the XGBoost classifier to build a predictive model and further developed an exposomic risk score (ERS) for risk stratification.
RESULTS
During a 15.3-year median follow-up, 8881 participants (1.77%) developed ADRD, including 4000 with Alzheimer's disease.
ExWAS identified 76 exposures after Bonferroni correction. The prediction model achieved area under the curve (AUC) = 0.718, outperforming demographics+apolipoprotein E (APOE) status alone (AUC = 0.678). The ERS stratified ADRD risk (highest vs lowest quartile hazard ratio [HR] = 2.97, 95% confidence interval [CI]: 2.59–3.41).
DISCUSSION
The ERS has the potential to contribute to clinically relevant prevention strategies for ADRD."
Fig. 1 Analytic workflow of the study.
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