Identifying genetic variants associated with sugar intake and appraising the genetic correlations with cardiovascular outcomes
(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.
(Less)
- author
- Janzi, Suzanne
LU
; Ramne, Stina
LU
; Kou, Minghao
; Lu, Xinmei
; Stubbendorff, Anna
LU
; Ke, Chaofu
; Borné, Yan
LU
; Qi, Lu
and Sonestedt, Emily
LU
- organization
- publishing date
- 2025-09-11
- 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}},
}