Diet-responsive proteogenomic effects following short-term restriction of animal products in humans

Abstract

The effect of diet on genetic regulation in humans remains largely unexplored. Here, we investigate gene-diet interactions in a unique group of healthy individuals (N = 200) who alternate between omnivory and dietary restriction of animal products for religious reasons. Using longitudinal proteomic and genotype data, we identify diet-responsive cis-pQTLs and highlight regulatory effects on LBR and MSRA, proteins involved in cholesterol and methionine metabolism respectively. LBR-associated cis-pQTL rs74148404 colocalizes with obesity exclusively under dietary restriction, suggesting diet-dependent modulation of genetic risk. We also show that a diet-dependent cis-pQTL for metabolic regulator FGF21 colocalizes with eosinophil and platelet traits pointing to diet-sensitive immunometabolic signalling. By parallel profiling of a continuously omnivorous control group (N = 211), we uncover seasonally dynamic genetic regulation for proteins linked to apoptosis in immune system pathways (MAVS, CASP3, PDLIM7, IL12RB1), effects likely masked by animal product restriction. These findings reveal dynamic diet- and season-sensitive regulatory mechanisms with implications for precision nutrition and individualized disease prevention strategies, and underscore the need to integrate environmental context into genetic studies of health and disease.

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BibTeX RIS

BibTeX

@article{simistiras2026dietresponsive,
  title = {{Diet-responsive proteogenomic effects following short-term restriction of animal products in humans}},
  author = {Alexandros Simistiras and Ozvan Bocher and Christina Emmanouil and Anargyros Skoulakis and Stavros Glentis and Nikolaos Scarmeas and Eleftheria Zeggini and Konstantinos Rouskas and Antigone Dimas},
  journal = {Nature Communications},
  year = {2026},
  month = aug,
  doi = {10.1038/s41467-026-76379-6},
  url = {https://hal.science/hal-05773979v1},
  note = {CC BY-NC-ND 4.0},
}

RIS

TY  - JOUR
TI  - Diet-responsive proteogenomic effects following short-term restriction of animal products in humans
AU  - Alexandros Simistiras
AU  - Ozvan Bocher
AU  - Christina Emmanouil
AU  - Anargyros Skoulakis
AU  - Stavros Glentis
AU  - Nikolaos Scarmeas
AU  - Eleftheria Zeggini
AU  - Konstantinos Rouskas
AU  - Antigone Dimas
PY  - 2026
DA  - 2026/08/08
JO  - Nature Communications
DO  - 10.1038/s41467-026-76379-6
UR  - https://hal.science/hal-05773979v1
AB  - The effect of diet on genetic regulation in humans remains largely unexplored. Here, we investigate gene-diet interactions in a unique group of healthy individuals (N = 200) who alternate between omnivory and dietary restriction of animal products for religious reasons. Using longitudinal proteomic and genotype data, we identify diet-responsive cis-pQTLs and highlight regulatory effects on LBR and MSRA, proteins involved in cholesterol and methionine metabolism respectively. LBR-associated cis-pQTL rs74148404 colocalizes with obesity exclusively under dietary restriction, suggesting diet-dependent modulation of genetic risk. We also show that a diet-dependent cis-pQTL for metabolic regulator FGF21 colocalizes with eosinophil and platelet traits pointing to diet-sensitive immunometabolic signalling. By parallel profiling of a continuously omnivorous control group (N = 211), we uncover seasonally dynamic genetic regulation for proteins linked to apoptosis in immune system pathways (MAVS, CASP3, PDLIM7, IL12RB1), effects likely masked by animal product restriction. These findings reveal dynamic diet- and season-sensitive regulatory mechanisms with implications for precision nutrition and individualized disease prevention strategies, and underscore the need to integrate environmental context into genetic studies of health and disease.
SN  - 2041-1723
SN  - 2041-1723
ER  -

Abstract

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