Triangulating population, individual, and genetic evidence for priority setting in structurally heterogeneous blocs: metabolic risk factors for stroke in the Shanghai Cooperation Organisation
- 1Xuanwu hospital, Capital Medical University
Abstract
BACKGROUND Regional stroke-prevention priorities usually rest on what a bloc’s members share. Where members span multiple Global Burden of Disease (GBD) super-regions and genetic ancestry groups, population, individual, and genetic evidence face different transportability limits, and earlier combined studies did not prespecify what counts as disagreement. METHODS We studied the Shanghai Cooperation Organisation, which spans four super-regions and five ancestry groups and is land-contiguous. For five metabolic risk factors we triangulated GBD 2023 attributable fractions of stroke DALYs in ten states, incident stroke among 7896 adults in the China Health and Retirement Longitudinal Study (2011–18; SHRs per 1 SD), and subtype-specific Mendelian randomisation in three ancestries. An explicit rule set, with one pre-submission amendment, classified convergence and divergence by whether a listed mechanism accounted for it. FINDINGS High systolic blood pressure converged: 53–71% of attributable DALYs, the strongest cohort exposure (SHR 1·37, 95% CI 1·26–1·48), and genetically supported in both ancestries. LDL cholesterol (GBD attribution restricted to ischaemic stroke; European genetic evidence for that subtype; no cohort association) and body-mass index (last in attribution but second in the cohort, with a 1·80-fold [1·48–2·18] gradient inside the 20–25 kg/m² minimum-risk window) showed structural discordance. The cohort lacked subtype data to establish LDL dilution. Fasting glucose and kidney dysfunction diverged without such a mechanism. INTERPRETATION Systolic blood pressure had the strongest cross-stream support. LDL cholesterol and body-mass index require qualified interpretation; fasting glucose and kidney dysfunction could not be ranked reliably. The framework identifies where priorities require scrutiny. FUNDING None.
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BibTeX
@misc{wang2026triangulating,
title = {{Triangulating population, individual, and genetic evidence for priority setting in structurally heterogeneous blocs: metabolic risk factors for stroke in the Shanghai Cooperation Organisation}},
author = {X. Wang and M. Li and J. Zhang and H. Zhang and Y. Ma},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.26364374},
url = {https://www.medrxiv.org/content/10.64898/2026.09.30.26364374v1},
note = {Public domain},
}
RIS
TY - UNPB
TI - Triangulating population, individual, and genetic evidence for priority setting in structurally heterogeneous blocs: metabolic risk factors for stroke in the Shanghai Cooperation Organisation
AU - X. Wang
AU - M. Li
AU - J. Zhang
AU - H. Zhang
AU - Y. Ma
PY - 2026
DA - 2026/09/30
PB - medRxiv
DO - 10.64898/2026.09.30.26364374
UR - https://www.medrxiv.org/content/10.64898/2026.09.30.26364374v1
AB - BACKGROUND Regional stroke-prevention priorities usually rest on what a bloc’s members share. Where members span multiple Global Burden of Disease (GBD) super-regions and genetic ancestry groups, population, individual, and genetic evidence face different transportability limits, and earlier combined studies did not prespecify what counts as disagreement. METHODS We studied the Shanghai Cooperation Organisation, which spans four super-regions and five ancestry groups and is land-contiguous. For five metabolic risk factors we triangulated GBD 2023 attributable fractions of stroke DALYs in ten states, incident stroke among 7896 adults in the China Health and Retirement Longitudinal Study (2011–18; SHRs per 1 SD), and subtype-specific Mendelian randomisation in three ancestries. An explicit rule set, with one pre-submission amendment, classified convergence and divergence by whether a listed mechanism accounted for it. FINDINGS High systolic blood pressure converged: 53–71% of attributable DALYs, the strongest cohort exposure (SHR 1·37, 95% CI 1·26–1·48), and genetically supported in both ancestries. LDL cholesterol (GBD attribution restricted to ischaemic stroke; European genetic evidence for that subtype; no cohort association) and body-mass index (last in attribution but second in the cohort, with a 1·80-fold [1·48–2·18] gradient inside the 20–25 kg/m² minimum-risk window) showed structural discordance. The cohort lacked subtype data to establish LDL dilution. Fasting glucose and kidney dysfunction diverged without such a mechanism. INTERPRETATION Systolic blood pressure had the strongest cross-stream support. LDL cholesterol and body-mass index require qualified interpretation; fasting glucose and kidney dysfunction could not be ranked reliably. The framework identifies where priorities require scrutiny. FUNDING None.
ER -