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@ARTICLE{PeruchetNoray:295908,
author = {L. Peruchet-Noray and N. Dimou and R. Cordova and E.
Fontvieille and A. Jansana and Q. Gan and M. Breeur and H.
Baurecht and P. Bohmann and J. Konzok and M. J. Stein and C.
C. Dahm and N. R. Zilhão and L. Mellemkjær and A.
Tjønneland and R. Kaaks$^*$ and V. Katzke$^*$ and E.
Inan-Eroglu and M. B. Schulze and G. Masala and S. Sieri and
V. Simeon and G. Matullo and E. Molina-Montes and P. Amiano
and M.-D. Chirlaque and A. Gasque and J. Atkins and K.
Smith-Byrne and P. Ferrari and V. Viallon and A. Agudo and
M. J. Gunter and C. Bonet and H. Freisling and R.
Carreras-Torres},
title = {{N}ature or nurture: genetic and environmental predictors
of adiposity gain in adults.},
journal = {EBioMedicine},
volume = {111},
issn = {2352-3964},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2024-02721},
pages = {105510},
year = {2025},
note = {Volume 111, January 2025, 105510},
abstract = {Previous prediction models for adiposity gain have not yet
achieved sufficient predictive ability for clinical
relevance. We investigated whether traditional and genetic
factors accurately predict adiposity gain.A 5-year gain of
$≥5\%$ in body mass index (BMI) and waist-to-hip ratio
(WHR) from baseline were predicted in mid-late adulthood
individuals (median of 55 years old at baseline).
Proportional hazards models were fitted in 245,699
participants from the European Prospective Investigation
into Cancer and Nutrition (EPIC) cohort to identify robust
environmental predictors. Polygenic risk scores (PRS) of 5
proxies of adiposity [BMI, WHR, and three body shape
phenotypes (PCs)] were computed using genetic weights from
an independent cohort (UK Biobank). Environmental and
genetic models were validated in 29,953 EPIC
participants.Environmental models presented a remarkable
predictive ability (AUCBMI: 0.69, $95\%$ CI: 0.68-0.70;
AUCWHR: 0.75, $95\%$ CI: 0.74-0.77). The genetic geographic
distribution for WHR and PC1 (overall adiposity) showed
higher predisposition in North than South Europe. Predictive
ability of PRSs was null (AUC: ∼0.52) and did not improve
when combined with environmental models. However, PRSs of
BMI and PC1 showed some prediction ability for BMI gain from
self-reported BMI at 20 years old to baseline observation
(early adulthood) (AUC: 0.60-0.62).Our study indicates that
environmental models to discriminate European individuals at
higher risk of adiposity gain can be integrated in standard
prevention protocols. PRSs may play a robust role in
predicting adiposity gain at early rather than mid-late
adulthood suggesting a more important role of genetic
factors in this life period.French National Cancer Institute
$(INCA_N°2019-176)$ 1220, German Research Foundation (BA
5459/2-1), Instituto de Salud Carlos III (Miguel Servet
Program CP21/00058).},
keywords = {Adiposity gain (Other) / Environmental factors (Other) /
Polygenic risk scores (Other) / Prediction (Other)},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39689375},
doi = {10.1016/j.ebiom.2024.105510},
url = {https://inrepo02.dkfz.de/record/295908},
}