Gaps in Population Life Course Phenotype Trajectories Underlying Major Noncommunicable Diseases: A Scoping Review.
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INTRODUCTION: The life course phenotypic pathways leading to noncommunicable diseases (NCDs) provide information needed to plan and test preventive interventions. However, most NCD-relevant phenotypes are not routinely measured until diagnosis and their pre-clinical trajectories are therefore not in linked population datasets. OBJECTIVES: In the context of planning phenotypic collection waves in an Australian early and pre-midlife mega-cohort, we aimed to undertake (1) a scoping review to identify knowledge availability and gaps and (2) a comparative map of trajectories from available data. METHODS: We searched PubMed and MEDLINE (September 2024) for trajectory studies on phenotypes underlying NCDs with the highest late life disease burden (excluding cancer and back pain, with no clear precursor phenotypes): cardiovascular, chronic obstructive pulmonary and kidney diseases, diabetes, falls, hearing and vision loss, and dementia. Eligible studies had ≥3 timepoints spanning ≥5 years in childhood or ≥10 years in adulthood. Using the R ggplot package, we fitted loess curves to create lifetime trajectory visualisations in absolute values and units standardised for comparison. RESULTS: From 3770 abstracts, we included 36 studies. Most (n == 19) examined cardiovascular trajectories, collectively spanning ages 5-105 years for blood pressure. Ten studies reported cognition trajectories, but could not be synthesised due to measurement diversity. Twelve studies mapped lung, glucose, kidney or musculoskeletal phenotypes but with discontinuities at varying life stages. No studies tracked vision or hearing trajectories. Our syntheses confirmed some known trajectory patterns, such as peaking of musculoskeletal phenotypes in early adulthood and the rise in cardiovascular and glucose markers beyond healthy ranges from midlife. CONCLUSIONS: Our mapping confirmed expected patterns for some phenotypes, but highlighted significant gaps for others on pathways to high-burden NCDs. If long-running population cohorts collectively tracked all major phenotypes over time, embedded real-world or simulated trials could accelerate progress in prevention and treatment across all major NCDs.