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Klaver"],"award-info":[{"award-number":["Ammodo Award to C.C.W. Klaver"]}]},{"name":"Dutch Organization for Scientific Research","award":["Vidi Innovational Research Award 016.096.309"],"award-info":[{"award-number":["Vidi Innovational Research Award 016.096.309"]}]},{"name":"Dutch Organization for Scientific Research","award":["FP\/2007-2013"],"award-info":[{"award-number":["FP\/2007-2013"]}]},{"name":"Dutch Organization for Scientific Research","award":["016.Vici.170.024 to AIdH"],"award-info":[{"award-number":["016.Vici.170.024 to AIdH"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Insights into the pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness, point towards a complex interplay of genetic and lifestyle factors triggering various systemic pathways. This study aimed to characterize metabolomic profiles for AMD and to evaluate their position in the trias with genetics and lifestyle. This study included 5923 individuals from five European studies. Blood metabolomics were assessed using a nuclear magnetic resonance platform of 146 metabolites. Associations were studied using regression analyses. A genetic risk score (GRS) was calculated using \u03b2-values of 49 AMD variants, a lifestyle risk score (LRS) using smoking and diet data, and a metabolite risk score (MRS) using metabolite values. We identified 61 metabolites associated with early-intermediate AMD, of which 94% were lipid-related, with higher levels of HDL-subparticles and apolipoprotein-A1, and lower levels of VLDL-subparticles, triglycerides, and fatty acids (false discovery rate (FDR) p-value &lt; 1.4 \u00d7 10\u22122). Late AMD was associated with lower levels of the amino acids histidine, leucine, valine, tyrosine, and phenylalanine, and higher levels of the ketone bodies acetoacetate and 3-hydroxybutyrate (FDR p-value &lt; 1.5 \u00d7 10\u22123). A favorable lifestyle characterized by a healthy diet was associated with higher levels of amino acids and lower levels of ketone bodies, while an unfavorable lifestyle, including smoking, showed opposite effects (FDR p-value &lt; 2.7 \u00d7 10\u22122). The MRS mediated 5% of the effect of the GRS and 20% of that of the LRS on late AMD. Our findings show that metabolomic profiles differ between AMD stages and show that blood metabolites mostly reflect lifestyle. The severity-specific profiles spur further interest into the systemic effects related to disease conversion.<\/jats:p>","DOI":"10.3390\/metabo13060701","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T16:18:43Z","timestamp":1685204323000},"page":"701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Systemic Metabolomics in a Framework of Genetics and Lifestyle in Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"13","author":[{"given":"Eric F.","family":"Thee","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Epidemiology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130lhan E.","family":"Acar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna M.","family":"Colijn","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Epidemiology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda A.","family":"Meester-Smoor","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Epidemiology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Verzijden","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara J.","family":"Baart","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Biostatistics, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5203-235X","authenticated-orcid":false,"given":"Mohamed A.","family":"Jarboui","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute for Ophthalmic Research, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Department of Ophthalmology, University Eye Clinic, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Fauser","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Cologne, 50937 Cologne, Germany"},{"name":"Hoffman-La Roche AG, 4070 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carel B.","family":"Hoyng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2209-2113","authenticated-orcid":false,"given":"Marius","family":"Ueffing","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute for Ophthalmic Research, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Department of Ophthalmology, University Eye Clinic, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0634-5408","authenticated-orcid":false,"given":"Anneke I.","family":"den Hollander","sequence":"additional","affiliation":[{"name":"AbbVie, Genomics Research center, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline C. W.","family":"Klaver","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Epidemiology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Institute of Molecular and Clinical Ophthalmology, University of Basel, 4070 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e144","DOI":"10.1016\/S2214-109X(20)30489-7","article-title":"Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: The Right to Sight: An analysis for the Global Burden of Disease Study","volume":"9","author":"Blindness","year":"2021","journal-title":"Lancet Glob. 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Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.ophtha.2020.11.024","article-title":"Genetic Risk, Lifestyle, and Age-Related Macular Degeneration in Europe: The EYE-RISK Consortium","volume":"128","author":"Colijn","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_7","first-page":"1604","article-title":"Development of a Genotype Assay for Age-Related Macular Degeneration: The EYE-RISK Consortium","volume":"128","author":"Acar","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.3945\/ajcn.115.111047","article-title":"Adherence to a Mediterranean diet, genetic susceptibility, and progression to advanced macular degeneration: A prospective cohort study","volume":"102","author":"Merle","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ophtha.2018.08.006","article-title":"Mediterranean Diet and Incidence of Advanced Age-Related Macular Degeneration: The EYE-RISK Consortium","volume":"126","author":"Merle","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ajo.2018.09.036","article-title":"Intake of Vegetables, Fruit, and Fish is Beneficial for Age-Related Macular Degeneration","volume":"198","author":"Buitendijk","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1167\/iovs.61.14.13","article-title":"Metabolomics in Age-Related Macular Degeneration: A Systematic Review","volume":"61","author":"Hou","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ophtha.2017.08.008","article-title":"Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers","volume":"125","author":"Lains","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.preteyeres.2018.11.002","article-title":"Metabolomics in the study of retinal health and disease","volume":"69","author":"Lains","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Brown, C.N., Green, B.D., Thompson, R.B., den Hollander, A.I., Lengyel, I., and Eye-Risk Consortium (2018). Metabolomics and Age-Related Macular Degeneration. Metabolites, 9.","DOI":"10.3390\/metabo9010004"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Osborn, M.P., Park, Y., Parks, M.B., Burgess, L.G., Uppal, K., Lee, K., Jones, D.P., and Brantley, M.A. (2013). Metabolome-wide association study of neovascular age-related macular degeneration. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072737"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kersten, E., Dammeier, S., Ajana, S., Groenewoud, J.M.M., Codrea, M., Klose, F., Lechanteur, Y.T., Fauser, S., Ueffing, M., and Delcourt, C. (2019). Metabolomics in serum of patients with non-advanced age-related macular degeneration reveals aberrations in the glutamine pathway. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0218457"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1007\/s00109-020-01994-9","article-title":"Pyruvate dehydrogenase kinase\/lactate axis: A therapeutic target for neovascular age-related macular degeneration identified by metabolomics","volume":"98","author":"Lambert","year":"2020","journal-title":"J. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100017","DOI":"10.1016\/j.xops.2021.100017","article-title":"Genomic-Metabolomic Associations Support the Role of LIPC and Glycerophospholipids in Age-Related Macular Degeneration","volume":"1","author":"Lains","year":"2021","journal-title":"Ophthalmol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.preteyeres.2018.12.003","article-title":"On the origin of proteins in human drusen: The meet, greet and stick hypothesis","volume":"70","author":"Bergen","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.survophthal.2017.05.003","article-title":"Systemic and ocular fluid compounds as potential biomarkers in age-related macular degeneration","volume":"63","author":"Kersten","year":"2018","journal-title":"Surv. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/j.ophtha.2020.06.020","article-title":"Integrating Metabolomics, Genomics, and Disease Pathways in Age-Related Macular Degeneration: The EYE-RISK Consortium","volume":"127","author":"Acar","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s10654-015-0098-2","article-title":"Ophthalmic epidemiology in Europe: The \u201cEuropean Eye Epidemiology\u201d (E3) consortium","volume":"31","author":"Delcourt","year":"2016","journal-title":"Eur. J. Epidemiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6611","DOI":"10.1038\/s41598-019-43144-3","article-title":"Genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration","volume":"9","author":"Heesterbeek","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.oret.2020.04.014","article-title":"Genotype- and Phenotype-Based Subgroups in Geographic Atrophy Secondary to Age-Related Macular Degeneration: The EYE-RISK Consortium","volume":"4","author":"Biarnes","year":"2020","journal-title":"Ophthalmol. Retin."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/aos.13883","article-title":"The European Eye Epidemiology spectral-domain optical coherence tomography classification of macular diseases for epidemiological studies","volume":"97","author":"Gattoussi","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.ophtha.2019.09.035","article-title":"Incomplete Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration: Classification of Atrophy Meeting Report 4","volume":"127","author":"Guymer","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1167\/tvst.9.2.26","article-title":"Performance of Classification Systems for Age-Related Macular Degeneration in the Rotterdam Study","volume":"9","author":"Thee","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/ije\/dyaa178","article-title":"The effects of eight serum lipid biomarkers on age-related macular degeneration risk: A Mendelian randomization study","volume":"50","author":"Han","year":"2021","journal-title":"Int. J. Epidemiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lains, I., Chung, W., Kelly, R.S., Gil, J., Marques, M., Barreto, P., Murta, J.N., Kim, I.K., Vavvas, D.G., and Miller, J.B. (2019). Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts. Metabolites, 9.","DOI":"10.3390\/metabo9070127"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1021\/acs.jproteome.8b00877","article-title":"Urine Nuclear Magnetic Resonance (NMR) Metabolomics in Age-Related Macular Degeneration","volume":"18","author":"Lains","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/ng.1073","article-title":"Genome-wide association study identifies multiple loci influencing human serum metabolite levels","volume":"44","author":"Kettunen","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00726-009-0269-0","article-title":"Amino acids: Metabolism, functions, and nutrition","volume":"37","author":"Wu","year":"2009","journal-title":"Amino Acids"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-3-030-45328-2_3","article-title":"Amino Acids in Circulatory Function and Health","volume":"1265","author":"Durante","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/cxo.12015","article-title":"Retinal amino acid neurochemistry in health and disease","volume":"96","author":"Kalloniatis","year":"2013","journal-title":"Clin. Exp. Optom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"20570","DOI":"10.1074\/jbc.M114.565457","article-title":"The retinal pigment epithelium utilizes fatty acids for ketogenesis","volume":"289","author":"Adijanto","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8038","DOI":"10.1074\/jbc.M116.770784","article-title":"Phagocytosis-dependent ketogenesis in retinal pigment epithelium","volume":"292","author":"Dhingra","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1161\/CIRCULATIONAHA.114.013116","article-title":"Metabolite profiling and cardiovascular event risk: A prospective study of 3 population-based cohorts","volume":"131","author":"Wurtz","year":"2015","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.ophtha.2017.03.042","article-title":"Mendelian Randomization Implicates High-Density Lipoprotein Cholesterol-Associated Mechanisms in Etiology of Age-Related Macular Degeneration","volume":"124","author":"Burgess","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ophtha.2018.09.045","article-title":"Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration: Evidence from the EYE-RISK and European Eye Epidemiology Consortia","volume":"126","author":"Colijn","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1053\/jcrc.2000.7900","article-title":"Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis","volume":"15","author":"Umpierrez","year":"2000","journal-title":"J. Crit. Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41433-021-01780-y","article-title":"Dyslipidemia in age-related macular degeneration","volume":"36","author":"Lin","year":"2022","journal-title":"Eye"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jcrc.2015.12.019","article-title":"Role of albumin in diseases associated with severe systemic inflammation: Pathophysiologic and clinical evidence in sepsis and in decompensated cirrhosis","volume":"33","author":"Artigas","year":"2016","journal-title":"J. Crit. Care"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1007\/s00592-021-01755-1","article-title":"C-reactive protein-to-albumin ratio and 8-year incidence of type 2 diabetes: The Korean genome and epidemiology study","volume":"58","author":"Cho","year":"2021","journal-title":"Acta Diabetol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1161\/CIRCGENETICS.114.000223","article-title":"Integrated metabolomics and genomics: Systems approaches to biomarkers and mechanisms of cardiovascular disease","volume":"8","author":"Shah","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.3945\/ajcn.113.076133","article-title":"The food metabolome: A window over dietary exposure","volume":"99","author":"Scalbert","year":"2014","journal-title":"Am. J. Clin. 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