biostudies-literatureHou TInnovative Research Team of High-level Local Universities in ShanghaiShanghai Eastern Talent PlanNational Natural Science Foundation of ChinaNoncommunicable Chronic Diseases-National Science and Technology Major Project of Chinae70065https://www.ebi.ac.uk/biostudies/studies/S-EPMC12266772biostudies-literatureUnknown24(7)Identifying factors affecting lifespan, including genes or proteins, enables effective interventions. We prioritized potential drug targets and provided insights into biological pathways for healthy longevity by integrating Mendelian randomization, cohort, and experimental studies. We identified causal effects of tissue-specific genetic transcripts and serum protein levels on three longevity outcomes: the parental lifespan, the top 1% and 10% extreme longevity, utilizing Mendelian randomization and multi-traits colocalization, combining the latest genetics data of gene expression (eQTLGen and GTEx) and proteomics (4746 proteins from five studies). We then evaluated associations of these potential genetic targets with mortality risk and life expectancy in the UK Biobank cohort. We performedAging cellIdentifying PDAP1 as a Biological Target on Human Longevity: Integration of Mendelian Randomization, Cohort, and Cell Experiments Validation Study.PMC12266772822708592024ZD05315002024ZD05315012024ZD0531502824708872023ZD05089012023ZD05089028208810291857205Xu MSha ZZhu ZZhu YHu WHou TZhao ZLi MNing GZheng JWang QWang TLu JWang WDai HXu YYe JBi YfalseIdentifying PDAP1 as a Biological Target on Human Longevity: Integration of Mendelian Randomization, Cohort, and Cell Experiments Validation Study.Identifying factors affecting lifespan, including genes or proteins, enables effective interventions. We prioritized potential drug targets and provided insights into biological pathways for healthy longevity by integrating Mendelian randomization, cohort, and experimental studies. We identified causal effects of tissue-specific genetic transcripts and serum protein levels on three longevity outcomes: the parental lifespan, the top 1% and 10% extreme longevity, utilizing Mendelian randomization and multi-traits colocalization, combining the latest genetics data of gene expression (eQTLGen and GTEx) and proteomics (4746 proteins from five studies). We then evaluated associations of these potential genetic targets with mortality risk and life expectancy in the UK Biobank cohort. We performed2025-01-01T00:00:00Z2025 Jul2026-07-15T06:25:26.028Z2025-08-30T03:05:39.053ZS-EPMC122667724021168110.1111/acel.70065