Proteomic signatures of BMI generalize across ancestries and reveal cardiometabolic heterogeneity beyond measured BMI
- 1Brigham and Womens Hospital
Abstract
Plasma proteomic scores for body mass index have been derived primarily in European populations, and it is unclear whether these scores are generalizable and useful in other ancestries. Here, we show that plasma proteomic BMI scores developed in participants of European, East Asian, South Asian and African ancestries from the UK Biobank (UKBB; N=50,621) and the South African Middle-Aged Soweto Cohort (MASC; N=948) are portable across ancestries, explain up to 48.7% of trait variance and significantly predict incident obesity. We identified eight protein biomarkers common across all scores, six of which showed causal associations with BMI in Mendelian randomization analyses and were associated with BMI across the Olink (UKBB, MASC) and SomaScan platforms (Qatar Biobank; N= 2410). Discrepancy analysis between the high predicted proteomic BMI and low measured BMI revealed metabolically unhealthy normal weight (MUNW) individuals, with higher visceral fat, elevated triglycerides, and low insulin sensitivity. Thus, plasma proteomic BMI scores may enhance the precision of cardiometabolic risk stratification across diverse populations.
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BibTeX
@misc{muti2026proteomic,
title = {{Proteomic signatures of BMI generalize across ancestries and reveal cardiometabolic heterogeneity beyond measured BMI}},
author = {M. Muti and Y. Ilboudo and U. Aliyu and C. Zhang and L. Ware and M. Chong and L. K. Micklesfield and J. H. Goedecke and R. Ntozini and G. Pare and M. H. Cho and M. Ramsay and A. P. Morris and P. W. Franks and A. B. Kamiza and S. A. Norris and O. M. E. Albagha and M. Moll and T. Chikowore},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.05.26362276},
url = {https://www.medrxiv.org/content/10.64898/2026.09.05.26362276v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Proteomic signatures of BMI generalize across ancestries and reveal cardiometabolic heterogeneity beyond measured BMI
AU - M. Muti
AU - Y. Ilboudo
AU - U. Aliyu
AU - C. Zhang
AU - L. Ware
AU - M. Chong
AU - L. K. Micklesfield
AU - J. H. Goedecke
AU - R. Ntozini
AU - G. Pare
AU - M. H. Cho
AU - M. Ramsay
AU - A. P. Morris
AU - P. W. Franks
AU - A. B. Kamiza
AU - S. A. Norris
AU - O. M. E. Albagha
AU - M. Moll
AU - T. Chikowore
PY - 2026
DA - 2026/09/05
PB - medRxiv
DO - 10.64898/2026.09.05.26362276
UR - https://www.medrxiv.org/content/10.64898/2026.09.05.26362276v1
AB - Plasma proteomic scores for body mass index have been derived primarily in European populations, and it is unclear whether these scores are generalizable and useful in other ancestries. Here, we show that plasma proteomic BMI scores developed in participants of European, East Asian, South Asian and African ancestries from the UK Biobank (UKBB; N=50,621) and the South African Middle-Aged Soweto Cohort (MASC; N=948) are portable across ancestries, explain up to 48.7% of trait variance and significantly predict incident obesity. We identified eight protein biomarkers common across all scores, six of which showed causal associations with BMI in Mendelian randomization analyses and were associated with BMI across the Olink (UKBB, MASC) and SomaScan platforms (Qatar Biobank; N= 2410). Discrepancy analysis between the high predicted proteomic BMI and low measured BMI revealed metabolically unhealthy normal weight (MUNW) individuals, with higher visceral fat, elevated triglycerides, and low insulin sensitivity. Thus, plasma proteomic BMI scores may enhance the precision of cardiometabolic risk stratification across diverse populations.
ER -