Pseudo-observations of longevity improve detection of resilience-associated genes in the Radiation Late Effects Cohort of rhesus macaques.

Pseudo-observations of Restricted Mean Survival Time in Macaca mulatta linked variant burden in PCDHGA5/PCDHGA3/PCDHGB2/PCDHA11/PSENEN to myocardial fibrosis severity.

• Why it matters: Survival modeling in long primate studies is hindered by non-proportional hazards, heavy censoring, and loss-to-follow-up, limiting detection of resilience-linked genetic signals.
• What they did: In the Wake Forest Non-Human Primate Radiation Late Effects Cohort, whole-exome GEMMA association for longevity was combined with GSEA, then CADD score-weighted SKAT-O tested cadherin and integrin pathway leading-edge genes against necropsy fibrosis severity.
• The result: The cadherin/integrin variant burdens were associated with necropsy fibrosis severity, supporting that pseudo-observation–based survival modeling can recover biologically relevant resilience genes under radiation plus aging and Western-style diet stressors.

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