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Article|12 Aug 2025|OPEN
Untargeted metabolomic genome-wide association study reveals genetic and biochemical insights into polyphenols of apple fruit 
Jun Song1 , , Beatrice Amyotte1 , Leslie Campbell Palmer1 , Melinda Vinqvist-Tymchuk1 , Kyra Dougherty2 and Letitia Da Ros,3
1Agriculture and Agri-Food Canada, Kentville Research and Development Centre, 32 Main Street, Kentville, Nova Scotia, B4N 1J5, Canada
2Agriculture and Agri-Food Canada, Fredericton Research and Development Centre, 95 Innovation Rd, Fredericton, New Brunswick, E3B 4Z7, Canada
3Agriculture and Agri-Food Canada, Summerland Research and Development Centre, 4200 Highway #97, South, Summerland, British Columbia, V0H 1Z0, Canada
*Corresponding author. E-mail: jun.song@agr.gc.ca

Horticulture Research 12,
Article number: uhaf159 (2025)
doi: https://doi.org/10.1093/hr/uhaf159
Views: 1442

Received: 12 Oct 2024
Accepted: 10 Jun 2025
Published online: 12 Aug 2025

Abstract

Apple (Malus × domestica) is one of the most popular fruits grown and consumed worldwide, contributing to human health with significant amounts of polyphenols and other bioactive compounds, and providing positive impacts to the economy and society. Understanding the diversity and inheritance of health-active compounds in apple can provide novel selection criteria for future breeding and cultivar development, as consumers increasingly prioritize the health benefits of their food choices. We therefore conducted an untargeted metabolomic analysis using ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) to investigate thousands of semipolar chemicals, mainly phenolic compounds, in 439 diverse apple accessions, and quantified 2066 features in positive ion mode. To identify key areas of genetic control for apple metabolite abundance, we performed a metabolomic genome-wide association study (mGWAS) on the quantified mass features using ~280 000 single nucleotide polymorphisms (SNPs). The mGWAS revealed >630 significant loci with hotspots for various groups of known and unknown phenolic compounds including flavonols on Chromosome 1, dihydrochalcones on Chromosome 5, and flavanols on Chromosomes 15 and 16. The most significant hotspot on Chromosome 16 included bHLH and C2H2 transcription factors that may play a role in controlling the abundance and complexity of phenolic compounds through regulation of the flavonoid biosynthesis pathway. Our analysis links the apple metabolome with candidate genes and biosynthetic mechanisms and establishes a foundation for marker-assisted breeding and gene editing to improve and modify phenolic compounds in apple for marketability and the benefit of human health.