{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:21:36Z","timestamp":1790774496030,"version":"4.1.0"},"reference-count":56,"publisher":"Elsevier BV","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["634479"],"award-info":[{"award-number":["634479"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013669","name":"Ionis Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013669","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["VICL170.024"],"award-info":[{"award-number":["VICL170.024"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aaojournal.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ophthalmology"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1016\/j.ophtha.2020.06.020","type":"journal-article","created":{"date-parts":[[2020,6,14]],"date-time":"2020-06-14T09:37:57Z","timestamp":1592127477000},"page":"1693-1709","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":83,"title":["Integrating Metabolomics, Genomics, and Disease Pathways in Age-Related Macular Degeneration"],"prefix":"10.1016","volume":"127","author":[{"given":"\u0130lhan E.","family":"Acar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Lores-Motta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna M.","family":"Colijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda A.","family":"Meester-Smoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Verzijden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1494-5764","authenticated-orcid":false,"given":"Audrey","family":"Cougnard-Gregoire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soufiane","family":"Ajana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedicte M.J.","family":"Merle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"de Breuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Heesterbeek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7693-0728","authenticated-orcid":false,"given":"Erik","family":"van den Akker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed R.","family":"Daha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte","family":"Claes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pauleikhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7381-1547","authenticated-orcid":false,"given":"Hans-Werner","family":"Hense","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia M.","family":"van Duijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Fauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carel B.","family":"Hoyng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Delcourt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline C.W.","family":"Klaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessel E.","family":"Galesloot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke I.","family":"den Hollander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Arango-Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Armento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Badura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav","family":"Bhatia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shomi S.","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Biarn\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Borrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia M.","family":"Calado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Dammeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta De la","family":"Cerda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Diaz-Corrales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Diether","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Emri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Endermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia L.","family":"Ferraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00edriam","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Honisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Kilger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elod","family":"Kortvely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Lastrucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanno","family":"Langen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imre","family":"Lengyel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil","family":"Luthert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Mon\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everson","family":"Nogoceke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tunde","family":"Peto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Pool","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Rodriguez-Bocanegra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Thee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Ueffing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl U.","family":"Ulrich Bartz-Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Zumbansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ophtha.2020.06.020_bib1","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S0140-6736(18)31550-2","article-title":"Age-related macular degeneration","volume":"392","author":"Mitchell","year":"2018","journal-title":"The Lancet"},{"key":"10.1016\/j.ophtha.2020.06.020_bib2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ng.3448","article-title":"A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants","volume":"48","author":"Fritsche","year":"2016","journal-title":"Nat Genet"},{"key":"10.1016\/j.ophtha.2020.06.020_bib3","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1001\/jamaophthalmol.2018.0504","article-title":"Incidence of and Risk Factors Associated With Age-Related Macular Degeneration: Four-Year Follow-up From the ALIENOR Study","volume":"136","author":"Saunier","year":"2018","journal-title":"Jama Ophthalmol"},{"key":"10.1016\/j.ophtha.2020.06.020_bib4","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":"10.1016\/j.ophtha.2020.06.020_bib5","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/ceo.13343","article-title":"Role of diet and food intake in age-related macular degeneration: a systematic review","volume":"47","author":"Chapman","year":"2019","journal-title":"Clin Exp Ophthalmol"},{"key":"10.1016\/j.ophtha.2020.06.020_bib6","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":"10.1016\/j.ophtha.2020.06.020_bib7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1136\/bjo.2005.073643","article-title":"Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation","volume":"90","author":"Khan","year":"2006","journal-title":"Br J Ophthalmol"},{"key":"10.1016\/j.ophtha.2020.06.020_bib8","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1006\/exer.2001.1094","article-title":"Complement activation and inflammatory processes in Drusen formation and age related macular degeneration","volume":"73","author":"Johnson","year":"2001","journal-title":"Exp Eye Res"},{"key":"10.1016\/j.ophtha.2020.06.020_bib9","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S1350-9462(01)00010-6","article-title":"An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration","volume":"20","author":"Hageman","year":"2001","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.ophtha.2020.06.020_bib10","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":"10.1016\/j.ophtha.2020.06.020_bib11","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1111\/j.1476-5381.2012.02081.x","article-title":"Cardiovascular disease risk reduction by raising HDL cholesterol--current therapies and future opportunities","volume":"167","author":"Mahdy Ali","year":"2012","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.ophtha.2020.06.020_bib12","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.preteyeres.2018.04.006","article-title":"A new perspective on lipid research in age-related macular degeneration","volume":"67","author":"van Leeuwen","year":"2018","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.ophtha.2020.06.020_bib13","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0177749","article-title":"Human plasma metabolomics in age-related macular degeneration (AMD) using nuclear magnetic resonance spectroscopy","volume":"12","author":"Lains","year":"2017","journal-title":"Plos One"},{"key":"10.1016\/j.ophtha.2020.06.020_bib14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0072737","article-title":"Metabolome-wide association study of neovascular age-related macular degeneration","volume":"8","author":"Osborn","year":"2013","journal-title":"Plos One"},{"key":"10.1016\/j.ophtha.2020.06.020_bib15","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12886-017-0555-7","article-title":"Plasma metabolomic study in Chinese patients with wet age-related macular degeneration","volume":"17","author":"Luo","year":"2017","journal-title":"Bmc Ophthalmol"},{"key":"10.1016\/j.ophtha.2020.06.020_bib16","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":"10.1016\/j.ophtha.2020.06.020_bib17","doi-asserted-by":"crossref","first-page":"38342","DOI":"10.1038\/srep38342","article-title":"Analysis of the Serum Lipid Profile in Polypoidal Choroidal Vasculopathy","volume":"6","author":"Li","year":"2016","journal-title":"Sci Rep"},{"key":"10.1016\/j.ophtha.2020.06.020_bib18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3390\/metabo9070127","article-title":"Human plasma metabolomics in age-related macular degeneration: Meta-analysis of two cohorts","volume":"9","author":"La\u00edns","year":"2019","journal-title":"Metabolites"},{"key":"10.1016\/j.ophtha.2020.06.020_bib19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0218457","article-title":"Metabolomics in serum of patients with non-advanced age-related macular degeneration reveals aberrations in the glutamine pathway","volume":"14","author":"Kersten","year":"2019","journal-title":"Plos One"},{"key":"10.1016\/j.ophtha.2020.06.020_bib20","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":"10.1016\/j.ophtha.2020.06.020_bib21","doi-asserted-by":"crossref","first-page":"5525","DOI":"10.1167\/iovs.10-6827","article-title":"Evaluation of serum lipid concentrations and genetic variants at high-density lipoprotein metabolism loci and TIMP3 in age-related macular degeneration","volume":"52","author":"Fauser","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2020.06.020_bib22","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1007\/s12603-010-0131-9","article-title":"Nutrition and age-related eye diseases: the Alienor (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) Study","volume":"14","author":"Delcourt","year":"2010","journal-title":"J Nutr Health Aging"},{"key":"10.1016\/j.ophtha.2020.06.020_bib23","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1080\/09286580802105830","article-title":"LOC387715, smoking and their prognostic impact on visual functional status in age-related macular degeneration-The Muenster Aging and Retina Study (MARS) cohort","volume":"15","author":"Neuner","year":"2008","journal-title":"Ophthalmic Epidemiol"},{"key":"10.1016\/j.ophtha.2020.06.020_bib24","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1001\/archopht.123.11.1501","article-title":"Inflammatory markers in age-related maculopathy: cross-sectional analysis from the Muenster Aging and Retina Study","volume":"123","author":"Dasch","year":"2005","journal-title":"Arch Ophthalmol"},{"key":"10.1016\/j.ophtha.2020.06.020_bib25","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1007\/s10654-017-0321-4","article-title":"The Rotterdam Study: 2018 update on objectives, design and main results","volume":"32","author":"Ikram","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"10.1016\/j.ophtha.2020.06.020_bib26","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1001\/archopht.121.4.519","article-title":"The risk and natural course of age-related maculopathy: follow-up at 6 1\/2 years in the Rotterdam study","volume":"121","author":"van Leeuwen","year":"2003","journal-title":"Arch Ophthalmol"},{"key":"10.1016\/j.ophtha.2020.06.020_bib27","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1161\/CIRCGENETICS.114.000216","article-title":"Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics","volume":"8","author":"Soininen","year":"2015","journal-title":"Circ Cardiovasc Genet"},{"key":"10.1016\/j.ophtha.2020.06.020_bib28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3389\/fbioe.2015.00023","article-title":"Analytical methods in untargeted metabolomics: state of the art in 2015","volume":"3","author":"Alonso","year":"2015","journal-title":"Front Bioeng Biotechnol"},{"key":"10.1016\/j.ophtha.2020.06.020_bib29","first-page":"40","article-title":"meta: An R package for meta-analysis","volume":"7","author":"Schwarzer","year":"2007","journal-title":"R News"},{"key":"10.1016\/j.ophtha.2020.06.020_bib30","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate - a Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc B"},{"key":"10.1016\/j.ophtha.2020.06.020_bib31","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/ng.3643","article-title":"A reference panel of 64,976 haplotypes for genotype imputation","volume":"48","author":"McCarthy","year":"2016","journal-title":"Nat Genet"},{"key":"10.1016\/j.ophtha.2020.06.020_bib32","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Genomes Project","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ophtha.2020.06.020_bib33","doi-asserted-by":"crossref","unstructured":"de Breuk A, Acar IE, Kersten E, et al. EYE-RISK Consortium. Development of a Genotype Assay for Age-Related Macular Degeneration: The EYE-RISK Consortium. Ophthalmology. 2020 Jul 24:S0161-6420(20)30725-9. https:\/\/doi.org\/10.1016\/j.ophtha.2020.07.037. Online ahead of print.","DOI":"10.1016\/j.ophtha.2020.07.037"},{"key":"10.1016\/j.ophtha.2020.06.020_bib34","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/humu.23247","article-title":"Haplotype reference consortium panel: Practical implications of imputations with large reference panels","volume":"38","author":"Iglesias","year":"2017","journal-title":"Hum Mutat"},{"key":"10.1016\/j.ophtha.2020.06.020_bib35","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/mp.2016.101","article-title":"Exome-sequencing in a large population-based study reveals a rare Asn396Ser variant in the LIPG gene associated with depressive symptoms","volume":"22","author":"Amin","year":"2017","journal-title":"Mol Psychiatry"},{"key":"10.1016\/j.ophtha.2020.06.020_bib36","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/j.ophtha.2018.03.040","article-title":"Whole-Exome Sequencing in Age-Related Macular Degeneration Identifies Rare Variants in COL8A1, a Component of Bruch's Membrane","volume":"125","author":"Corominas","year":"2018","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ophtha.2020.06.020_bib37","doi-asserted-by":"crossref","first-page":"26568","DOI":"10.1038\/srep26568","article-title":"A Novel Complotype Combination Associates with Age-Related Macular Degeneration and High Complement Activation Levels in vivo","volume":"6","author":"Paun","year":"2016","journal-title":"Sci Rep"},{"key":"10.1016\/j.ophtha.2020.06.020_bib38","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.ophtha.2017.12.023","article-title":"Genome-Wide Association Study Reveals Variants in CFH and CFHR4 Associated with Systemic Complement Activation: Implications in Age-Related Macular Degeneration","volume":"125","author":"Lores-Motta","year":"2018","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ophtha.2020.06.020_bib39","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/1756-0500-4-169","article-title":"Temperature and time stability of whole blood lactate: implications for feasibility of pre-hospital measurement","volume":"4","author":"Seymour","year":"2011","journal-title":"BMC Res Notes"},{"key":"10.1016\/j.ophtha.2020.06.020_bib40","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13073-017-0418-0","article-title":"Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits","volume":"9","author":"Grassmann","year":"2017","journal-title":"Genome Med"},{"key":"10.1016\/j.ophtha.2020.06.020_bib41","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jalz.2018.01.003","article-title":"Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts","volume":"14","author":"Tynkkynen","year":"2018","journal-title":"Alzheimers Dement"},{"key":"10.1016\/j.ophtha.2020.06.020_bib42","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.atherosclerosis.2010.02.020","article-title":"Long-term coronary heart disease risk associated with very-low-density lipoprotein cholesterol in Chinese: the results of a 15-Year Chinese Multi-Provincial Cohort Study (CMCS)","volume":"211","author":"Ren","year":"2010","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.ophtha.2020.06.020_bib43","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":"10.1016\/j.ophtha.2020.06.020_bib44","doi-asserted-by":"crossref","first-page":"101222","DOI":"10.1016\/j.redox.2019.101222","article-title":"HDL subclass proteomic analysis and functional implication of protein dynamic change during HDL maturation","volume":"24","author":"Zhang","year":"2019","journal-title":"Redox Biol"},{"key":"10.1016\/j.ophtha.2020.06.020_bib45","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0160240","article-title":"Olive Oil Consumption and Age-Related Macular Degeneration: The Alienor Study","volume":"11","author":"Cougnard-Gregoire","year":"2016","journal-title":"Plos One"},{"key":"10.1016\/j.ophtha.2020.06.020_bib46","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1167\/iovs.14-13916","article-title":"Circulating omega-3 Fatty acids and neovascular age-related macular degeneration","volume":"55","author":"Merle","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2020.06.020_bib47","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":"10.1016\/j.ophtha.2020.06.020_bib48","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":"10.1016\/j.ophtha.2020.06.020_bib49","doi-asserted-by":"crossref","DOI":"10.1093\/jn\/136.1.269S","article-title":"Branched-chain amino acids activate key enzymes in protein synthesis after physical exercise","volume":"136","author":"Blomstrand","year":"2006","journal-title":"J Nutr"},{"key":"10.1016\/j.ophtha.2020.06.020_bib50","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.1073\/pnas.0812874106","article-title":"Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites","volume":"106","author":"Wikoff","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ophtha.2020.06.020_bib51","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nature24661","article-title":"A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites","volume":"551","author":"Dodd","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.ophtha.2020.06.020_bib52","doi-asserted-by":"crossref","first-page":"8212063","DOI":"10.1155\/2016\/8212063","article-title":"Relation between Age-Related Macular Degeneration and Cardiovascular Events and Mortality: A Systematic Review and Meta-Analysis","volume":"2016","author":"Wang","year":"2016","journal-title":"Biomed Res Int"},{"key":"10.1016\/j.ophtha.2020.06.020_bib53","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":"10.1016\/j.ophtha.2020.06.020_bib54","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ophtha.2011.07.056","article-title":"Risk alleles in CFH and ARMS2 are independently associated with systemic complement activation in age-related macular degeneration","volume":"119","author":"Smailhodzic","year":"2012","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ophtha.2020.06.020_bib55","first-page":"6852","article-title":"High fish oil diet promotes liver inflammation and activates the complement system","volume":"17","author":"Jin","year":"2018","journal-title":"Mol Med Rep"},{"key":"10.1016\/j.ophtha.2020.06.020_bib56","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1038\/ijo.2017.120","article-title":"Dietary medium-chain saturated fatty acids induce gene expression of energy metabolism-related pathways in adipose tissue of abdominally obese subjects","volume":"41","author":"Matualatupauw","year":"2017","journal-title":"Int J Obes (Lond)"}],"container-title":["Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161642020305613?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161642020305613?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:16:26Z","timestamp":1778717786000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0161642020305613"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":56,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["S0161642020305613"],"URL":"https:\/\/doi.org\/10.1016\/j.ophtha.2020.06.020","relation":{},"ISSN":["0161-6420"],"issn-type":[{"value":"0161-6420","type":"print"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Integrating Metabolomics, Genomics, and Disease Pathways in Age-Related Macular Degeneration","name":"articletitle","label":"Article Title"},{"value":"Ophthalmology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ophtha.2020.06.020","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 by the American Academy of OphthalmologyThis is an open access article under the CC BY-NC-ND license (<inter-ref xlink: href=http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/>http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/<\/inter-ref>).","name":"copyright","label":"Copyright"}]}}