Genome-wide association study of the taste and hedonic ratings of the low-calorie sweetener acesulfame potassium

Abstract Acesulfame potassium (Ace-K) is a low-calorie sweetener (LCS) widely used as an ingredient in foods and beverages and an excipient in pediatric medicines. While prior candidate gene studies have established that genetic variants in bitter taste receptor (TAS2R) genes are associated with var...

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Main Authors: Mengyuan Kan, Luis R. Saraiva, Liang-Dar Hwang, Elizabeth D. Lowenthal, Blanca E. Himes, Julie A. Mennella
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05739-x
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author Mengyuan Kan
Luis R. Saraiva
Liang-Dar Hwang
Elizabeth D. Lowenthal
Blanca E. Himes
Julie A. Mennella
author_facet Mengyuan Kan
Luis R. Saraiva
Liang-Dar Hwang
Elizabeth D. Lowenthal
Blanca E. Himes
Julie A. Mennella
author_sort Mengyuan Kan
collection DOAJ
description Abstract Acesulfame potassium (Ace-K) is a low-calorie sweetener (LCS) widely used as an ingredient in foods and beverages and an excipient in pediatric medicines. While prior candidate gene studies have established that genetic variants in bitter taste receptor (TAS2R) genes are associated with variation in the taste of Ace-K, we sought to identify genetic contributions to its taste using a genome-wide association study (GWAS) of 141 adult panelists who rated the taste of an aqueous solution of Ace-K using the general labelled magnitude scale (gLMS) and its palatability using the hedonic gLMS. To determine whether GWAS-identified associations with Ace-K generalized to a more complex stimulus, panelists also rated the taste of a pediatric medicine that contains Ace-K as an excipient (Children’s Motrin™). We identified that a TAS2R-containing locus on chromosome 12 was associated with bitterness ratings of Ace-K (p-values < 5 × 10− 8), and the lead SNP rs2708381 in this locus was associated with the sweetness intensity of Children’s Motrin™ (p-value = 0.001). SNP rs2708381 was also associated with perceived intensity ratings of another LCS, neohesperidine dihydrochalcone, in a replication GWAS of 1,757 panelists (p-value = 0.002). A locus within the gene ELMO1, which encodes engulfment and cell motility protein 1, was associated with hedonic ratings of Ace-K (p-values < 5 × 10− 8), and no genome-wide significant signals were observed for sweetness ratings. These findings identify a novel genetic locus containing TAS2R genes that contributes to personal differences in the taste of Ace-K, which may impact the acceptance of medicines, food, and beverages containing Ace-K. Clinical trials registration: Sensory evaluation of the taste of pediatric medicines (MEDTASTE); clinical trials registry number NCT03627351, registered on 13 August 2018.
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spelling doaj-art-a24f4d56bac54090833c43bbf65601992025-08-20T03:03:42ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-05739-xGenome-wide association study of the taste and hedonic ratings of the low-calorie sweetener acesulfame potassiumMengyuan Kan0Luis R. Saraiva1Liang-Dar Hwang2Elizabeth D. Lowenthal3Blanca E. Himes4Julie A. Mennella5Department of Biostatistics, Epidemiology and Informatics, University of PennsylvaniaSidra MedicineInstitute for Molecular Science, The University of QueenslandDepartment of Pediatrics, University of PennsylvaniaDepartment of Biostatistics, Epidemiology and Informatics, University of PennsylvaniaMonell Chemical Senses CenterAbstract Acesulfame potassium (Ace-K) is a low-calorie sweetener (LCS) widely used as an ingredient in foods and beverages and an excipient in pediatric medicines. While prior candidate gene studies have established that genetic variants in bitter taste receptor (TAS2R) genes are associated with variation in the taste of Ace-K, we sought to identify genetic contributions to its taste using a genome-wide association study (GWAS) of 141 adult panelists who rated the taste of an aqueous solution of Ace-K using the general labelled magnitude scale (gLMS) and its palatability using the hedonic gLMS. To determine whether GWAS-identified associations with Ace-K generalized to a more complex stimulus, panelists also rated the taste of a pediatric medicine that contains Ace-K as an excipient (Children’s Motrin™). We identified that a TAS2R-containing locus on chromosome 12 was associated with bitterness ratings of Ace-K (p-values < 5 × 10− 8), and the lead SNP rs2708381 in this locus was associated with the sweetness intensity of Children’s Motrin™ (p-value = 0.001). SNP rs2708381 was also associated with perceived intensity ratings of another LCS, neohesperidine dihydrochalcone, in a replication GWAS of 1,757 panelists (p-value = 0.002). A locus within the gene ELMO1, which encodes engulfment and cell motility protein 1, was associated with hedonic ratings of Ace-K (p-values < 5 × 10− 8), and no genome-wide significant signals were observed for sweetness ratings. These findings identify a novel genetic locus containing TAS2R genes that contributes to personal differences in the taste of Ace-K, which may impact the acceptance of medicines, food, and beverages containing Ace-K. Clinical trials registration: Sensory evaluation of the taste of pediatric medicines (MEDTASTE); clinical trials registry number NCT03627351, registered on 13 August 2018.https://doi.org/10.1038/s41598-025-05739-xAcesulfame-KLow-calorie sweetenersGeneral labelled magnitude scaleGenome-wide association studyPediatric medicinesTaste
spellingShingle Mengyuan Kan
Luis R. Saraiva
Liang-Dar Hwang
Elizabeth D. Lowenthal
Blanca E. Himes
Julie A. Mennella
Genome-wide association study of the taste and hedonic ratings of the low-calorie sweetener acesulfame potassium
Scientific Reports
Acesulfame-K
Low-calorie sweeteners
General labelled magnitude scale
Genome-wide association study
Pediatric medicines
Taste
title Genome-wide association study of the taste and hedonic ratings of the low-calorie sweetener acesulfame potassium
title_full Genome-wide association study of the taste and hedonic ratings of the low-calorie sweetener acesulfame potassium
title_fullStr Genome-wide association study of the taste and hedonic ratings of the low-calorie sweetener acesulfame potassium
title_full_unstemmed Genome-wide association study of the taste and hedonic ratings of the low-calorie sweetener acesulfame potassium
title_short Genome-wide association study of the taste and hedonic ratings of the low-calorie sweetener acesulfame potassium
title_sort genome wide association study of the taste and hedonic ratings of the low calorie sweetener acesulfame potassium
topic Acesulfame-K
Low-calorie sweeteners
General labelled magnitude scale
Genome-wide association study
Pediatric medicines
Taste
url https://doi.org/10.1038/s41598-025-05739-x
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