{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:55Z","timestamp":1785428095621,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["UM1 CA186107"],"award-info":[{"award-number":["UM1 CA186107"]}]},{"name":"NIH","award":["CA167552"],"award-info":[{"award-number":["CA167552"]}]},{"award":["UM1 CA186107"],"award-info":[{"award-number":["UM1 CA186107"]}],"id":[{"id":"https:\/\/ror.org\/044zkrt47","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CA167552"],"award-info":[{"award-number":["CA167552"]}],"id":[{"id":"https:\/\/ror.org\/044zkrt47","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korea government","doi-asserted-by":"publisher","award":["RS-2025-16068795"],"award-info":[{"award-number":["RS-2025-16068795"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Understanding the genetic basis of food consumption is a key step toward precision nutrition, viewed as a long-term future perspective. This study aimed to investigate genetic variants associated with grapefruit (Citrus paradisi) intake and to evaluate their potential relationship with obesity risk. Methods: A genome-wide association study (GWAS) was conducted on 19,653 European-ancestry participants from two prospective cohorts, the Nurses\u2019 Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). We employed a functional annotation strategy to select a suggestive locus for follow-up analysis, and computationally derived molecular docking simulations explored a plausible functional link between grapefruit\u2019s bioactive compounds and the candidate gene product. Results: Although falling short of the conventional threshold for genome-wide significance, a suggestive locus was prioritized on chromosome 14, with the lead single nucleotide polymorphism (SNP), rs2124 (p &lt; 5 \u00d7 10\u22126), located within the metabolic gene ADCK1 (aarF domain containing kinase 1). Molecular docking simulations supported a plausible mechanistic hypothesis, indicating that key bioactive compounds in grapefruit could bind with high affinity to the ADCK1 protein. Consistent with the GWAS finding, individuals with the CC genotype reported lower mean grapefruit intake. This genotype was also associated with other lifestyle factors, notably, lower physical activity in women. In age- and multivariate-adjusted models, the CC genotype was associated with a modestly increased risk of incident obesity in females, but not in males. Conclusions: Our exploratory findings suggest a prioritized candidate locus associated with grapefruit intake, and its link to obesity risk may be mediated by the metabolic gene ADCK1. However, given the lack of genome-wide significance and independent replication, these findings should be considered preliminary and exploratory. These hypothesis-generating results support the integration of genetics and dietary habits, warranting further mechanistic validation.<\/jats:p>","DOI":"10.3390\/nu18091319","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:54:08Z","timestamp":1776862448000},"page":"1319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Genome-Wide Association Study of Grapefruit Intake and Its Potential Link to Obesity Risk in US Cohorts"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5724-2217","authenticated-orcid":false,"given":"Ji Hyun","family":"Bae","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6061-2928","authenticated-orcid":false,"given":"Hyunju","family":"Kang","sequence":"additional","affiliation":[{"name":"School of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea"},{"name":"Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1475-2891-6-33","article-title":"Medicinal Importance of Grapefruit Juice and Its Interaction with Various Drugs","volume":"6","author":"Kiani","year":"2007","journal-title":"Nutr. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.metabol.2011.12.004","article-title":"The Effects of Daily Consumption of Grapefruit on Body Weight, Lipids, and Blood Pressure in Healthy, Overweight Adults","volume":"61","author":"Dow","year":"2012","journal-title":"Metab. Clin. Exp."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Saini, R.K., Ranjit, A., Sharma, K., Prasad, P., Shang, X., Gowda, K.G.M., and Keum, Y.-S. (2022). Bioactive Compounds of Citrus Fruits: A Review of Composition and Health Benefits of Carotenoids, Flavonoids, Limonoids, and Terpenes. Antioxidants, 11.","DOI":"10.3390\/antiox11020239"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kang, H., and Kim, B. (2023). Bioactive Compounds as Inhibitors of Inflammation, Oxidative Stress and Metabolic Dysfunctions via Regulation of Cellular Redox Balance and Histone Acetylation State. Foods, 12.","DOI":"10.3390\/foods12050925"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gropper, S.S. (2023). The Role of Nutrition in Chronic Disease. Nutrients, 15.","DOI":"10.3390\/nu15030664"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Emmerich, S.D., Fryar, C.D., Stierman, B., and Ogden, C.L. (2024). Obesity and Severe Obesity Prevalence in Adults: United States, August 2021\u2013August 2023; NCHS Data Brief, National Center for Health Statistics.","DOI":"10.15620\/cdc\/159281"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e25043","DOI":"10.2196\/25043","article-title":"Exploring the Potential of Personalized Dietary Advice for Health Improvement in Motivated Individuals with Premetabolic Syndrome: Pretest-Posttest Study","volume":"5","author":"Hoevenaars","year":"2021","journal-title":"JMIR Form. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.freeradbiomed.2025.02.033","article-title":"Identifying Genetic Overlaps in Obesity and Metabolic Disorders Unlocking Unique and Shared Mechanistic Insights","volume":"231","author":"Fu","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.molmed.2025.02.002","article-title":"Genetic Causes of Obesity: Mapping a Path Forward","volume":"31","author":"Loos","year":"2025","journal-title":"Trends Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Di\u00f3szegi, J., Llanaj, E., and \u00c1d\u00e1ny, R. (2019). Genetic Background of Taste Perception, Taste Preferences, and Its Nutritional Implications: A Systematic Review. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.01272"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1016\/j.tjnut.2025.06.001","article-title":"A Genome-Wide Association Study of Taste Liking in the Danish Population","volume":"155","author":"Haydar","year":"2025","journal-title":"J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bae, J.H., and Kang, H. (2024). Identification of Sweetness Preference-Related Single-Nucleotide Polymorphisms for Polygenic Risk Scores Associated with Obesity. Nutrients, 16.","DOI":"10.3390\/nu16172972"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bae, J.H., and Kang, H. (2024). Longitudinal Analysis of Sweet Taste Preference Through Genetic and Phenotypic Data Integration. Foods, 13.","DOI":"10.3390\/foods13213370"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1080\/09637486.2025.2596106","article-title":"Longitudinal Study on the Association between Salty Food Preference and Obesity Prevalence","volume":"77","author":"Bae","year":"2026","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wooding, S.P., and Ramirez, V.A. (2022). Global Population Genetics and Diversity in the TAS2R Bitter Taste Receptor Family. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.952299"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/emph\/eoab031","article-title":"Bitter Taste Receptors: Genes, Evolution and Health","volume":"9","author":"Wooding","year":"2021","journal-title":"Evol. Med. Public Health"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Singar, S., Nagpal, R., Arjmandi, B.H., and Akhavan, N.S. (2024). Personalized Nutrition: Tailoring Dietary Recommendations through Genetic Insights. Nutrients, 16.","DOI":"10.3390\/nu16162673"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1089\/jwh.1997.6.49","article-title":"The Nurses\u2019 Health Study: 20-Year Contribution to the Understanding of Health Among Women","volume":"6","author":"Colditz","year":"1997","journal-title":"J. Women\u2019s Health"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1093\/oxfordjournals.aje.a116211","article-title":"Reproducibility and Validity of an Expanded Self-Administered Semiquantitative Food Frequency Questionnaire among Male Health Professionals","volume":"135","author":"Rimm","year":"1992","journal-title":"Am. J. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/0140-6736(91)90542-W","article-title":"Prospective Study of Alcohol Consumption and Risk of Coronary Disease in Men","volume":"338","author":"Rimm","year":"1991","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1161\/CIRCGENETICS.111.960393","article-title":"Protein Interaction-Based Genome-Wide Analysis of Incident Coronary Heart Disease","volume":"4","author":"Jensen","year":"2011","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cornelis, M.C., Monda, K.L., Yu, K., Paynter, N., Azzato, E.M., Bennett, S.N., Berndt, S.I., Boerwinkle, E., Chanock, S., and Chatterjee, N. (2011). Genome-Wide Meta-Analysis Identifies Regions on 7p21 (AHR) and 15q24 (CYP1A2) as Determinants of Habitual Caffeine Consumption. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002033"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lindstr\u00f6m, S., Loomis, S., Turman, C., Huang, H., Huang, J., Aschard, H., Chan, A.T., Choi, H., Cornelis, M., and Curhan, G. (2017). A Comprehensive Survey of Genetic Variation in 20,691 Subjects from Four Large Cohorts. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173997"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jiang, L., Penney, K.L., Giovannucci, E., Kraft, P., and Wilson, K.M. (2018). A Genome-Wide Association Study of Energy Intake and Expenditure. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201555"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional Mapping and Annotation of Genetic Associations with FUMA","volume":"8","author":"Watanabe","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/s41588-018-0152-6","article-title":"Genome-Wide Association Meta-Analysis in 269,867 Individuals Identifies New Genetic and Functional Links to Intelligence","volume":"50","author":"Savage","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A General Framework for Estimating the Relative Pathogenicity of Human Genetic Variants","volume":"46","author":"Kircher","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1101\/gr.137323.112","article-title":"Annotation of Functional Variation in Personal Genomes Using RegulomeDB","volume":"22","author":"Boyle","year":"2012","journal-title":"Genome Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"GTEx Consortium, Ardlie, K.G., Deluca, D.S., Segr\u00e8, A.V., Sullivan, T.J., Young, T.R., Gelfand, E.T., Trowbridge, C.A., Maller, J.B., and Tukiainen, T. (2015). The Genotype-Tissue Expression (GTEx) Pilot Analysis: Multitissue Gene Regulation in Humans. Science, 348, 648\u2013660.","DOI":"10.1126\/science.1262110"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"D877","DOI":"10.1093\/nar\/gkv1340","article-title":"HaploReg v4: Systematic Mining of Putative Causal Variants, Cell Types, Regulators and Target Genes for Human Complex Traits and Disease","volume":"44","author":"Ward","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-Generation PLINK: Rising to the Challenge of Larger and Richer Datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","article-title":"METAL: Fast and Efficient Meta-Analysis of Genomewide Association Scans","volume":"26","author":"Willer","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107264","DOI":"10.1016\/j.fbio.2025.107264","article-title":"Food Bioscience Fisetin Attenuates Lipopolysaccharide-Induced Neuroinflammation by Modulating the Histone Deacetylase 3\u2014Nuclear Factor Erythroid 2\u2014Related Factor 2 Axis","volume":"71","author":"Jo","year":"2025","journal-title":"Food Biosci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Carri\u00f3n, R., Sorl\u00ed, J.V., Coltell, O., Pascual, E.C., Ortega-Azor\u00edn, C., Barrag\u00e1n, R., Gim\u00e9nez-Alba, I.M., Alvarez-Sala, A., Fit\u00f3, M., and Ordovas, J.M. (2021). Sweet Taste Preference: Relationships with Other Tastes, Liking for Sugary Foods and Exploratory Genome-Wide Association Analysis in Subjects with Metabolic Syndrome. Biomedicines, 10.","DOI":"10.3390\/biomedicines10010079"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Pilalis, E., Zisis, D., Andrinopoulou, C., Karamanidou, T., Antonara, M., Stavropoulos, T.G., and Chatziioannou, A. (2025). Genome-Wide Functional Annotation of Variants: A Systematic Review of State-of-the-Art Tools, Techniques and Resources. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1474026"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.nutres.2023.08.006","article-title":"Biological Activities of Naringenin: A Narrative Review Based on in Vitro and in Vivo Studies","volume":"119","year":"2023","journal-title":"Nutr. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.4014\/jmb.2410.10006","article-title":"A Comprehensive Review of Naringenin, a Promising Phytochemical with Therapeutic Potential","volume":"34","author":"Shin","year":"2024","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Stabrauskiene, J., Kopustinskiene, D.M., Lazauskas, R., and Bernatoniene, J. (2022). Naringin and Naringenin: Their Mechanisms of Action and the Potential Anticancer Activities. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071686"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jfda.2016.11.008","article-title":"Chemistry and Health Effects of Furanocoumarins in Grapefruit","volume":"25","author":"Hung","year":"2017","journal-title":"J. Food Drug Anal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1073\/pnas.90.2.442","article-title":"The Conserved Lysine of the Catalytic Domain of Protein Kinases Is Actively Involved in the Phosphotransfer Reaction and Not Required for Anchoring ATP","volume":"90","author":"Carrera","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"D368","DOI":"10.1093\/nar\/gkad1011","article-title":"AlphaFold Protein Structure Database in 2024: Providing Structure Coverage for over 214 Million Protein Sequences","volume":"52","author":"Varadi","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s12078-010-9079-8","article-title":"Vegetable Intake in College-Aged Adults Is Explained by Oral Sensory Phenotypes and TAS2R38 Genotype","volume":"3","author":"Duffy","year":"2010","journal-title":"Chemosens. Percept."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liem, D.G., and Russell, C.G. (2019). The Influence of Taste Liking on the Consumption of Nutrient Rich and Nutrient Poor Foods. Front. Nutr., 6.","DOI":"10.3389\/fnut.2019.00174"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.cofs.2021.07.001","article-title":"Genetic Variation in Sensation Affects Food Liking and Intake","volume":"42","author":"Feeney","year":"2021","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"22179","DOI":"10.3402\/fnr.v58.22179","article-title":"Consumption of Grapefruit Is Associated with Higher Nutrient Intakes and Diet Quality among Adults, and More Favorable Anthropometrics in Women, NHANES 2003\u20132008","volume":"58","author":"Murphy","year":"2014","journal-title":"Food Nutr. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100002","DOI":"10.1016\/j.fufo.2020.100002","article-title":"Managing Obesity through Natural Polyphenols: A Review","volume":"1\u20132","author":"Singh","year":"2020","journal-title":"Futur. Foods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.1016\/j.tjnut.2024.08.024","article-title":"Perspective: Key Considerations When Developing and Publishing Dietary Interventions for Human Clinical Trials","volume":"154","author":"Leidy","year":"2024","journal-title":"J. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.compbiolchem.2018.04.002","article-title":"Targeting Natural Compounds against HER2 Kinase Domain as Potential Anticancer Drugs Applying Pharmacophore Based Molecular Modelling Approaches","volume":"74","author":"Rampogu","year":"2018","journal-title":"Comput. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kang, H. (2023). Regulation of Acetylation States by Nutrients in the Inhibition of Vascular Inflammation and Atherosclerosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119338"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/dvdy.66","article-title":"Functional Analysis of Aarf Domain-Containing Kinase 1 in Drosophila melanogaster","volume":"248","author":"Wisidagama","year":"2019","journal-title":"Dev. Dyn."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Jacquet, N., and Zhao, Y. (2025). The ADCK Kinase Family: Key Regulators of Bioenergetics and Mitochondrial Function and Their Implications in Human Cancers. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125783"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/9\/1319\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:34:47Z","timestamp":1777005287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/9\/1319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":52,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["nu18091319"],"URL":"https:\/\/doi.org\/10.3390\/nu18091319","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]}}}