Biomarker Panel Selection Explains Heterogeneity in Allostatic Load-Mortality Risk: A Specification-Curve Analysis

The allostatic load (AL)-mortality association is well-established, yet published studies use at least 18 distinct calculation methods across 26 biomarkers, raising a fundamental question: does this association reflect a stable biological signal or an artifact of investigator choice? We applied the first multiverse specification-curve analysis of AL to two independent NHANES cohorts (NHANES III: n = 17,285; NHANES 2007-2010: n = 12,729) linked to the National Death Index through 2019, constructing 450 analytical specifications by systematically varying biomarker panel, scoring method, covariate configuration, and mortality outcome. Every cardiovascular mortality specification (100% of 150) and 93.3% of all-cause specifications produced statistically significant hazard ratios exceeding 1.0. Median HRs per 1-SD increment in AL were 1.22 (all-cause, pooled) and 1.36 (cardiovascular) -- numerically identical to Parker et al.s conventional meta-analytic estimate of 1.22. Biomarker panel composition explained 46% of between-specification variance, compared with 4% for covariate adjustment. A five-biomarker panel (SBP, BMI, HDL, HbA1c, creatinine) performed comparably to an 18-biomarker expanded panel, with 100% of specifications significant across both cohorts. The AL-mortality association is a robust biological signal; biomarker panel selection -- not covariate adjustment -- is the primary target for field-wide standardization.