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Identifying genetic variants associated with sugar intake and appraising the genetic correlations with cardiovascular outcomes

Janzi, Suzanne LU ; Ramne, Stina LU orcid ; Kou, Minghao ; Lu, Xinmei ; Stubbendorff, Anna LU orcid ; Ke, Chaofu ; Borné, Yan LU ; Qi, Lu and Sonestedt, Emily LU orcid (2025) In Clinical Nutrition 54. p.110-119
Abstract

BACKGROUND: The evidence linking sugar intake to cardiovascular disease risk remains largely inconclusive, with variations observed across different subgroups of sugar intake. In addition, studies on genetic markers of sugar intake are scarce, especially for different sugar subgroups.

OBJECTIVE: This genome-wide association study (GWAS) aimed to investigate genetic variants associated with the intake of free sugars and sweet-tasting sugars (i.e., sucrose and monosaccharides) and to explore the relationship between sugar intake and cardiovascular disease risk using genetic markers.

METHODS: We identified single-nucleotide polymorphisms (SNPs) associated with sugar intakes in two large cohorts: the Malmö Diet and Cancer Study... (More)

BACKGROUND: The evidence linking sugar intake to cardiovascular disease risk remains largely inconclusive, with variations observed across different subgroups of sugar intake. In addition, studies on genetic markers of sugar intake are scarce, especially for different sugar subgroups.

OBJECTIVE: This genome-wide association study (GWAS) aimed to investigate genetic variants associated with the intake of free sugars and sweet-tasting sugars (i.e., sucrose and monosaccharides) and to explore the relationship between sugar intake and cardiovascular disease risk using genetic markers.

METHODS: We identified single-nucleotide polymorphisms (SNPs) associated with sugar intakes in two large cohorts: the Malmö Diet and Cancer Study (n = 25,660) and the UK Biobank (n = 141,437). We further examined whether the associations were independent of Body Mass Index (BMI), smoking status, and educational level. Finally, we investigated the genetic correlations between sugar intake and cardiovascular outcomes using data from different populations.

RESULTS: For free sugar intake, GWAS-significant associations were found with SNPs in the FTO gene, in an intergenic region on chromosome 18, and near the FGF21 gene. For sweet-tasting sugar intake, the lead SNP was located near the FGF21 gene. The associations between sugar intake and the FTO SNPs were dependent on BMI, whereas this dependency was not observed for the FGF21-adjacent SNPs. Genetic correlations were found between both free sugar intake and sweet-tasting sugar intake and lower HDL cholesterol levels and heart failure risk, as well as higher log-triglyceride levels and risks of ischemic stroke and atrial fibrillation.

CONCLUSION: The findings of this study indicate associations mainly between SNPs near the FGF21 gene and the FTO gene and both free and sweet-tasting sugar intake. Genetic correlations were found between both free sugar intake and sweet-tasting sugar intake and lower HDL cholesterol levels and heart failure risk, as well as higher triglyceride levels and risks of ischemic stroke and atrial fibrillation.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Clinical Nutrition
volume
54
pages
110 - 119
publisher
Elsevier
external identifiers
  • scopus:105018015524
  • pmid:41056811
ISSN
1532-1983
DOI
10.1016/j.clnu.2025.08.020
language
English
LU publication?
yes
additional info
Copyright © 2025. Published by Elsevier Ltd.
id
f1938b04-0849-4ae4-8155-db4c90b7eb9e
date added to LUP
2025-10-13 11:04:11
date last changed
2025-11-25 07:57:56
@article{f1938b04-0849-4ae4-8155-db4c90b7eb9e,
  abstract     = {{<p>BACKGROUND: The evidence linking sugar intake to cardiovascular disease risk remains largely inconclusive, with variations observed across different subgroups of sugar intake. In addition, studies on genetic markers of sugar intake are scarce, especially for different sugar subgroups.</p><p>OBJECTIVE: This genome-wide association study (GWAS) aimed to investigate genetic variants associated with the intake of free sugars and sweet-tasting sugars (i.e., sucrose and monosaccharides) and to explore the relationship between sugar intake and cardiovascular disease risk using genetic markers.</p><p>METHODS: We identified single-nucleotide polymorphisms (SNPs) associated with sugar intakes in two large cohorts: the Malmö Diet and Cancer Study (n = 25,660) and the UK Biobank (n = 141,437). We further examined whether the associations were independent of Body Mass Index (BMI), smoking status, and educational level. Finally, we investigated the genetic correlations between sugar intake and cardiovascular outcomes using data from different populations.</p><p>RESULTS: For free sugar intake, GWAS-significant associations were found with SNPs in the FTO gene, in an intergenic region on chromosome 18, and near the FGF21 gene. For sweet-tasting sugar intake, the lead SNP was located near the FGF21 gene. The associations between sugar intake and the FTO SNPs were dependent on BMI, whereas this dependency was not observed for the FGF21-adjacent SNPs. Genetic correlations were found between both free sugar intake and sweet-tasting sugar intake and lower HDL cholesterol levels and heart failure risk, as well as higher log-triglyceride levels and risks of ischemic stroke and atrial fibrillation.</p><p>CONCLUSION: The findings of this study indicate associations mainly between SNPs near the FGF21 gene and the FTO gene and both free and sweet-tasting sugar intake. Genetic correlations were found between both free sugar intake and sweet-tasting sugar intake and lower HDL cholesterol levels and heart failure risk, as well as higher triglyceride levels and risks of ischemic stroke and atrial fibrillation.</p>}},
  author       = {{Janzi, Suzanne and Ramne, Stina and Kou, Minghao and Lu, Xinmei and Stubbendorff, Anna and Ke, Chaofu and Borné, Yan and Qi, Lu and Sonestedt, Emily}},
  issn         = {{1532-1983}},
  language     = {{eng}},
  month        = {{09}},
  pages        = {{110--119}},
  publisher    = {{Elsevier}},
  series       = {{Clinical Nutrition}},
  title        = {{Identifying genetic variants associated with sugar intake and appraising the genetic correlations with cardiovascular outcomes}},
  url          = {{http://dx.doi.org/10.1016/j.clnu.2025.08.020}},
  doi          = {{10.1016/j.clnu.2025.08.020}},
  volume       = {{54}},
  year         = {{2025}},
}