{"entity": "researcher", "timestamp": "2026-08-11T14:49:24.968Z", "family": "McCarthy", "given": "Mark I", "initials": "MI", "orcid": "0000-0002-4393-0510", "affiliations": ["Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK.", "Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.", "Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK.", "Genentech, South San Francisco, CA, USA."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/5e44f4b1ca3a49cb8f83450ef9482e91.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/5e44f4b1ca3a49cb8f83450ef9482e91"}}, "publications": [{"entity": "publication", "iuid": "f9a66d44fe71490393256b7b3d96a56c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f9a66d44fe71490393256b7b3d96a56c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f9a66d44fe71490393256b7b3d96a56c"}}, "title": "Genetics meets proteomics: perspectives for large population-based studies.", "authors": [{"family": "Suhre", "given": "Karsten", "initials": "K", "orcid": "0000-0001-9638-3912", "researcher": {"href": "https://publications.scilifelab.se/researcher/4613b34ecf6d44119a1f806caa8281bf.json"}}, {"family": "McCarthy", "given": "Mark I", "initials": "MI", "orcid": "0000-0002-4393-0510", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e44f4b1ca3a49cb8f83450ef9482e91.json"}}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "Nat. Rev. Genet.", "issn": "1471-0064", "issn-l": "1471-0056", "volume": "22", "issue": "1", "pages": "19-37"}, "abstract": "Proteomic analysis of cells, tissues and body fluids has generated valuable insights into the complex processes influencing human biology. Proteins represent intermediate phenotypes for disease and provide insight into how genetic and non-genetic risk factors are mechanistically linked to clinical outcomes. Associations between protein levels and DNA sequence variants that colocalize with risk alleles for common diseases can expose disease-associated pathways, revealing novel drug targets and translational biomarkers. However, genome-wide, population-scale analyses of proteomic data are only now emerging. Here, we review current findings from studies of the plasma proteome and discuss their potential for advancing biomedical translation through the interpretation of genome-wide association analyses. We highlight the challenges faced by currently available technologies and provide perspectives relevant to their future application in large-scale biobank studies.", "doi": "10.1038/s41576-020-0268-2", "pmid": "32860016", "labels": {"Affinity Proteomics Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41576-020-0268-2"}], "notes": [], "created": "2020-12-10T19:03:43.347Z", "modified": "2021-11-10T12:28:05.295Z"}, {"entity": "publication", "iuid": "06bdda0e02974b29a11b5fc22fa91b3b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/06bdda0e02974b29a11b5fc22fa91b3b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/06bdda0e02974b29a11b5fc22fa91b3b"}}, "title": "Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus.", "authors": [{"family": "van Zuydam", "given": "Natalie R", "initials": "NR", "orcid": "0000-0002-9809-1398", "researcher": {"href": "https://publications.scilifelab.se/researcher/defa68cc40734fcdaffd7ba0aaad72b8.json"}}, {"family": "Ladenvall", "given": "Claes", "initials": "C", "orcid": "0000-0002-7501-6598", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c5c362dc308476195eb55d2e588ba60.json"}}, {"family": "Voight", "given": "Benjamin F", "initials": "BF", "orcid": "0000-0002-6205-9994", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3d9e9de96ee4983ba97efc14eb3d79b.json"}}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ", "orcid": "0000-0001-8506-3585", "researcher": {"href": "https://publications.scilifelab.se/researcher/8ac5060a3b37466dae002d4ad8f4d0ac.json"}}, {"family": "Fernandez-Tajes", "given": "Juan", "initials": "J", "orcid": "0000-0003-1515-2421", "researcher": {"href": "https://publications.scilifelab.se/researcher/dad51251fc8d42f793e4c991c4102667.json"}}, {"family": "Rayner", "given": "N William", "initials": "NW", "orcid": "0000-0003-0510-4792", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e3c7e5bd20348629ba3fe232fc2bcd2.json"}}, {"family": "Robertson", "given": "Neil R", "initials": "NR"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Vlachopoulou", "given": "Efthymia", "initials": "E"}, {"family": "Goel", "given": "Anuj", "initials": "A", "orcid": "0000-0003-2307-4021", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f16d9d2e2164938a12b027326c21316.json"}}, {"family": "Kleber", "given": "Marcus E", "initials": "ME"}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Kwee", "given": "Lydia Coulter", "initials": "LC", "orcid": "0000-0002-6997-8571", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa16042af5d84f11927203fc564e8fcb.json"}}, {"family": "Esko", "given": "T\u00f5nu", "initials": "T", "orcid": "0000-0003-1982-6569", "researcher": {"href": "https://publications.scilifelab.se/researcher/d72619c1e29d44e8b8454902d2af8d9e.json"}}, {"family": "Mihailov", "given": "Evelin", "initials": "E"}, {"family": "M\u00e4gi", "given": "Reedik", "initials": "R", "orcid": "0000-0002-2964-6011", "researcher": {"href": "https://publications.scilifelab.se/researcher/61f337c26b414b8fa30bf0fdb77368a1.json"}}, {"family": "Milani", "given": "Lili", "initials": "L", "orcid": "0000-0002-5323-3102", "researcher": {"href": "https://publications.scilifelab.se/researcher/dec8d00c4b9d43458c5c895b164695d5.json"}}, {"family": "Fischer", "given": "Krista", "initials": "K", "orcid": "0000-0002-3521-0599", "researcher": {"href": "https://publications.scilifelab.se/researcher/bcd45c97a9c2450c9c88adbd83d36b24.json"}}, {"family": "Kanoni", "given": "Stavroula", "initials": "S", "orcid": "0000-0002-1691-9615", "researcher": {"href": "https://publications.scilifelab.se/researcher/95f9c5fce1fe44719ef772eda9a4f5e4.json"}}, {"family": "Kumar", "given": "Jitender", "initials": "J"}, {"family": "Song", "given": "Ci", "initials": "C"}, {"family": "Hartiala", "given": "Jaana A", "initials": "JA", "orcid": "0000-0003-4883-9318", "researcher": {"href": "https://publications.scilifelab.se/researcher/f39400df71774cf8ae408eccbe34d981.json"}}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL", "orcid": "0000-0001-8057-3543", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbee4e5f6d10460cac50f00ee92d5bdf.json"}}, {"family": "Perola", "given": "Markus", "initials": "M", "orcid": "0000-0003-4842-1667", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef3cdf94ecb543f1a449a7704f8be7b2.json"}}, {"family": "Gieger", "given": "Christian", "initials": "C"}, {"family": "Peters", "given": "Annette", "initials": "A", "orcid": "0000-0001-6645-0985", "researcher": {"href": "https://publications.scilifelab.se/researcher/05465e52a0f6412e81752d2249af30de.json"}}, {"family": "Qu", "given": "Liming", "initials": "L"}, {"family": "Willems", "given": "Sara M", "initials": "SM", "orcid": "0000-0002-6803-3007", "researcher": {"href": "https://publications.scilifelab.se/researcher/307c8a9b3ab54ab586c7b000c110e76b.json"}}, {"family": "Doney", "given": "Alex S F", "initials": "ASF"}, {"family": "Morris", "given": "Andrew D", "initials": "AD"}, {"family": "Zheng", "given": "Yan", "initials": "Y", "orcid": "0000-0003-1129-3147", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0baf9bc398345709fcfe2f635c6d443.json"}}, {"family": "Sesti", "given": "Giorgio", "initials": "G", "orcid": "0000-0002-1618-7688", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c564dce3a584837a595ad7c9630092d.json"}}, {"family": "Hu", "given": "Frank B", "initials": "FB", "orcid": "0000-0002-8233-6274", "researcher": {"href": "https://publications.scilifelab.se/researcher/8cdf552612da400a9b3d72aaed260aa9.json"}}, {"family": "Qi", "given": "Lu", "initials": "L", "orcid": "0000-0002-8041-7791", "researcher": {"href": "https://publications.scilifelab.se/researcher/14b5a04081604f12859bb18b5e7c0f38.json"}}, {"family": "Laakso", "given": "Markku", "initials": "M", "orcid": "0000-0002-3394-7749", "researcher": {"href": "https://publications.scilifelab.se/researcher/13d8518be25141a296d7f2df5cccb4ee.json"}}, {"family": "Thorsteinsdottir", "given": "Unnur", "initials": "U"}, {"family": "Grallert", "given": "Harald", "initials": "H"}, {"family": "van Duijn", "given": "Cornelia", "initials": "C", "orcid": "0000-0002-2374-9204", "researcher": {"href": "https://publications.scilifelab.se/researcher/354ccf94e95f40da96e61c89a0a60adb.json"}}, {"family": "Reilly", "given": "Muredach P", "initials": "MP", "orcid": "0000-0002-3035-9386", "researcher": {"href": "https://publications.scilifelab.se/researcher/de249cb6c3774f04985a39ca9828b97e.json"}}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Deloukas", "given": "Panos", "initials": "P", "orcid": "0000-0001-9251-070X", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb59dbd2f2204d41b801c41188611a9e.json"}}, {"family": "Kathiresan", "given": "Sek", "initials": "S", "orcid": "0000-0002-3711-7101", "researcher": {"href": "https://publications.scilifelab.se/researcher/58fd968293e94da49c506c743a74222e.json"}}, {"family": "Metspalu", "given": "Andres", "initials": "A", "orcid": "0000-0002-3718-796X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd553a77a5a54258b4a4701f0e70a3f8.json"}}, {"family": "Shah", "given": "Svati H", "initials": "SH"}, {"family": "Sinisalo", "given": "Juha", "initials": "J", "orcid": "0000-0002-0169-5137", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fde24cdfda24aed83d888da0d9b6811.json"}}, {"family": "Salomaa", "given": "Veikko", "initials": "V", "orcid": "0000-0001-7563-5324", "researcher": {"href": "https://publications.scilifelab.se/researcher/f2396c578c254e39b66538c3033c9ce9.json"}}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ", "orcid": "0000-0002-3286-8133", "researcher": {"href": "https://publications.scilifelab.se/researcher/2227aaf274e8424f8408318f336f3bf1.json"}}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W"}, {"family": "Hazen", "given": "Stanley L", "initials": "SL", "orcid": "0000-0001-7124-6639", "researcher": {"href": "https://publications.scilifelab.se/researcher/abce9cd916c94667a73bc348ede57a01.json"}}, {"family": "Watkins", "given": "Hugh", "initials": "H", "orcid": "0000-0002-5287-9016", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ea10989397546f9a027f88bd491bb8b.json"}}, {"family": "Saleheen", "given": "Danish", "initials": "D"}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "Colhoun", "given": "Helen M", "initials": "HM", "orcid": "0000-0002-8345-3288", "researcher": {"href": "https://publications.scilifelab.se/researcher/e79cb60e3d734232b7cfad20c4f1c13e.json"}}, {"family": "Groop", "given": "Leif", "initials": "L"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI", "orcid": "0000-0002-4393-0510", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e44f4b1ca3a49cb8f83450ef9482e91.json"}}, {"family": "Palmer", "given": "Colin N A", "initials": "CNA", "orcid": "0000-0002-6415-6560", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a0f019dcb7a453a84480953a5514dd5.json"}}, {"family": "SUMMIT Steering Committee; CARDIOGRAMplusC4D Steering Committee*", "given": "", "initials": ""}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Circ Genom Precis Med", "issn": "2574-8300", "issn-l": "2574-8300", "volume": "13", "issue": "6", "pages": "e002769"}, "abstract": "Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).\r\n\r\nTo test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).\r\n\r\nNone of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.\r\n\r\nThis study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.", "doi": "10.1161/CIRCGEN.119.002769", "pmid": "33321069", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7748049"}], "notes": [], "created": "2021-01-07T17:01:51.462Z", "modified": "2021-12-07T13:47:48.005Z"}, {"entity": "publication", "iuid": "e81411b4717b4690acc189ae0314d13d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e81411b4717b4690acc189ae0314d13d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e81411b4717b4690acc189ae0314d13d"}}, "title": "Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts.", "authors": [{"family": "Atabaki-Pasdar", "given": "Naeimeh", "initials": "N", "orcid": "0000-0001-7229-1888", "researcher": {"href": "https://publications.scilifelab.se/researcher/42005ff304fd4e5d855a248db59f9256.json"}}, {"family": "Ohlsson", "given": "Mattias", "initials": "M", "orcid": "0000-0003-1145-4297", "researcher": {"href": "https://publications.scilifelab.se/researcher/6550861766f14999b5059457fed37baa.json"}}, {"family": "Vi\u00f1uela", "given": "Ana", "initials": "A", "orcid": "0000-0003-3771-8537", "researcher": {"href": "https://publications.scilifelab.se/researcher/e6551fc3132f4fa597378c565247a315.json"}}, {"family": "Frau", "given": "Francesca", "initials": "F"}, {"family": "Pomares-Millan", "given": "Hugo", "initials": "H", "orcid": "0000-0001-9245-4576", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a53517766c64538876c42890911aed7.json"}}, {"family": "Haid", "given": "Mark", "initials": "M", "orcid": "0000-0001-6118-1333", "researcher": {"href": "https://publications.scilifelab.se/researcher/a51bbc9e2ca34b75ba75e6b3be85da87.json"}}, {"family": "Jones", "given": "Angus G", "initials": "AG", "orcid": "0000-0002-0883-7599", "researcher": {"href": "https://publications.scilifelab.se/researcher/e61710036445440ea18c4cc05bbd8a0b.json"}}, {"family": "Thomas", "given": "E Louise", "initials": "EL", "orcid": "0000-0003-4235-4694", "researcher": {"href": "https://publications.scilifelab.se/researcher/186f6dee4a8a4e199e519199a62d4918.json"}}, {"family": "Koivula", "given": "Robert W", "initials": "RW", "orcid": "0000-0002-1646-4163", "researcher": {"href": "https://publications.scilifelab.se/researcher/29fa233507ea4e6190e70953cbb743a8.json"}}, {"family": "Kurbasic", "given": "Azra", "initials": "A", "orcid": "0000-0002-1910-2619", "researcher": {"href": "https://publications.scilifelab.se/researcher/64a6b0e38fdc43f59725c6013e9ffd75.json"}}, {"family": "Mutie", "given": "Pascal M", "initials": "PM"}, {"family": "Fitipaldi", "given": "Hugo", "initials": "H", "orcid": "0000-0001-5352-2134", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca2f9fb4ba1a42c59104097626568a97.json"}}, {"family": "Fernandez", "given": "Juan", "initials": "J"}, {"family": "Dawed", "given": "Adem Y", "initials": "AY", "orcid": "0000-0003-0224-2428", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1b08d70569c4ee98f6b174425a443a7.json"}}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "Forgie", "given": "Ian M", "initials": "IM", "orcid": "0000-0002-8800-6145", "researcher": {"href": "https://publications.scilifelab.se/researcher/bcf5280c81274cb3b983c00b20fbd0a7.json"}}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ"}, {"family": "Rutters", "given": "Femke", "initials": "F"}, {"family": "Cederberg", "given": "Henna", "initials": "H", "orcid": "0000-0003-2901-9373", "researcher": {"href": "https://publications.scilifelab.se/researcher/64ab64bd196c4dc88904a53826dda0e1.json"}}, {"family": "Chabanova", "given": "Elizaveta", "initials": "E"}, {"family": "Dale", "given": "Matilda", "initials": "M", "orcid": "0000-0002-5788-7744", "researcher": {"href": "https://publications.scilifelab.se/researcher/59306e7e902048829efb30599ee3d2b1.json"}}, {"family": "Masi", "given": "Federico De", "initials": "F", "orcid": "0000-0003-4859-4170", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb3d84bde37b4deb8838eb7b95762832.json"}}, {"family": "Thomas", "given": "Cecilia Engel", "initials": "CE", "orcid": "0000-0001-6201-6380", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a1156f987764218af202efbd76c31fd.json"}}, {"family": "Allin", "given": "Kristine H", "initials": "KH", "orcid": "0000-0002-6880-5759", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b7436fd7201456d9555235679ad0aa3.json"}}, {"family": "Hansen", "given": "Tue H", "initials": "TH", "orcid": "0000-0001-5948-8993", "researcher": {"href": "https://publications.scilifelab.se/researcher/c43c49838ac04c30ac2d92153e51f555.json"}}, {"family": "Heggie", "given": "Alison", "initials": "A"}, {"family": "Hong", "given": "Mun-Gwan", "initials": "MG"}, {"family": "Elders", "given": "Petra J M", "initials": "PJM", "orcid": "0000-0002-5907-7219", "researcher": {"href": "https://publications.scilifelab.se/researcher/4cf5e762102f4cc6a669b6d0989ab3a1.json"}}, {"family": "Kennedy", "given": "Gwen", "initials": "G", "orcid": "0000-0002-9856-3236", "researcher": {"href": "https://publications.scilifelab.se/researcher/28563ecc468548a4a75f127ffd3ab61b.json"}}, {"family": "Kokkola", "given": "Tarja", "initials": "T", "orcid": "0000-0002-3303-3912", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa456d442a7342238959b8ee46310319.json"}}, {"family": "Pedersen", "given": "Helle Krogh", "initials": "HK", "orcid": "0000-0001-9609-7377", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad86129a6eec49f1b0fe4ce09643c8a1.json"}}, {"family": "Mahajan", "given": "Anubha", "initials": "A", "orcid": "0000-0001-5585-3420", "researcher": {"href": "https://publications.scilifelab.se/researcher/194be8a851164e2ea4d004dd2febc9be.json"}}, {"family": "McEvoy", "given": "Donna", "initials": "D", "orcid": "0000-0003-1546-5567", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4455f5ace534325ba30494630686066.json"}}, {"family": "Pattou", "given": "Francois", "initials": "F"}, {"family": "Raverdy", "given": "Violeta", "initials": "V"}, {"family": "H\u00e4ussler", "given": "Ragna S", "initials": "RS", "orcid": "0000-0003-1664-8875", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca04d9b9132747efb7db0efb6e34756a.json"}}, {"family": "Sharma", "given": "Sapna", "initials": "S"}, {"family": "Thomsen", "given": "Henrik S", "initials": "HS"}, {"family": "Vangipurapu", "given": "Jagadish", "initials": "J", "orcid": "0000-0001-6657-2659", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc3c64aafa4841729040479765aae6f2.json"}}, {"family": "Vestergaard", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3090-269X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a79ddd7842e480f85b0a303125fdc9a.json"}}, {"family": "'t Hart", "given": "Leen M", "initials": "LM", "orcid": "0000-0003-4401-2938", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cb1193c2ad3419899ec86d9d95bf25d.json"}}, {"family": "Adamski", "given": "Jerzy", "initials": "J"}, {"family": "Musholt", "given": "Petra B", "initials": "PB"}, {"family": "Brage", "given": "Soren", "initials": "S", "orcid": "0000-0002-1265-7355", "researcher": {"href": "https://publications.scilifelab.se/researcher/2edeab82aa9f4513baa3dc724c0a4a88.json"}}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "Dermitzakis", "given": "Emmanouil", "initials": "E"}, {"family": "Frost", "given": "Gary", "initials": "G", "orcid": "0000-0003-0529-6325", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9312f44496b4bdb86ad9c5096aeb94c.json"}}, {"family": "Hansen", "given": "Torben", "initials": "T", "orcid": "0000-0001-8748-3831", "researcher": {"href": "https://publications.scilifelab.se/researcher/da403496660346079fc41975cae418d9.json"}}, {"family": "Laakso", "given": "Markku", "initials": "M"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Ridderstr\u00e5le", "given": "Martin", "initials": "M"}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Hattersley", "given": "Andrew T", "initials": "AT", "orcid": "0000-0001-5620-473X", "researcher": {"href": "https://publications.scilifelab.se/researcher/25dad832cfe041a79e35170e789e66c7.json"}}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Beulens", "given": "Joline W J", "initials": "JWJ"}, {"family": "Mari", "given": "Andrea", "initials": "A", "orcid": "0000-0002-1436-5591", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8b959c8980a4d108b602d82cd345ba6.json"}}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Gupta", "given": "Ramneek", "initials": "R", "orcid": "0000-0001-6841-6676", "researcher": {"href": "https://publications.scilifelab.se/researcher/445ec9fcd4a740a385550d10d19e8317.json"}}, {"family": "McCarthy", "given": "Mark I", "initials": "MI", "orcid": "0000-0002-4393-0510", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e44f4b1ca3a49cb8f83450ef9482e91.json"}}, {"family": "Pearson", "given": "Ewan R", "initials": "ER", "orcid": "0000-0001-9237-8585", "researcher": {"href": "https://publications.scilifelab.se/researcher/320eb6ae20014620ad8f69c3f7b216b3.json"}}, {"family": "Bell", "given": "Jimmy D", "initials": "JD", "orcid": "0000-0003-3804-1281", "researcher": {"href": "https://publications.scilifelab.se/researcher/74a9ddf1d40e4b4fb1614a89a220e143.json"}}, {"family": "Pavo", "given": "Imre", "initials": "I"}, {"family": "Franks", "given": "Paul W", "initials": "PW", "orcid": "0000-0002-0520-7604", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ebbf40c0f7e49dd8c75a2b6cbf27276.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "PLoS Med.", "issn": "1549-1676", "issn-l": "1549-1277", "volume": "17", "issue": "6", "pages": "e1003149"}, "abstract": "Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning.\n\nWe utilized the baseline data from IMI DIRECT, a multicenter prospective cohort study of 3,029 European-ancestry adults recently diagnosed with T2D (n = 795) or at high risk of developing the disease (n = 2,234). Multi-omics (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI-image-derived liver fat content (<5% or \u22655%) available for 1,514 participants. We applied LASSO (least absolute shrinkage and selection operator) to select features from the different layers of omics data and random forest analysis to develop the models. The prediction models included clinical and omics variables separately or in combination. A model including all omics and clinical variables yielded a cross-validated receiver operating characteristic area under the curve (ROCAUC) of 0.84 (95% CI 0.82, 0.86; p < 0.001), which compared with a ROCAUC of 0.82 (95% CI 0.81, 0.83; p < 0.001) for a model including 9 clinically accessible variables. The IMI DIRECT prediction models outperformed existing noninvasive NAFLD prediction tools. One limitation is that these analyses were performed in adults of European ancestry residing in northern Europe, and it is unknown how well these findings will translate to people of other ancestries and exposed to environmental risk factors that differ from those of the present cohort. Another key limitation of this study is that the prediction was done on a binary outcome of liver fat quantity (<5% or \u22655%) rather than a continuous one.\n\nIn this study, we developed several models with different combinations of clinical and omics data and identified biological features that appear to be associated with liver fat accumulation. In general, the clinical variables showed better prediction ability than the complex omics variables. However, the combination of omics and clinical variables yielded the highest accuracy. We have incorporated the developed clinical models into a web interface (see: https://www.predictliverfat.org/) and made it available to the community.\n\nClinicalTrials.gov NCT03814915.", "doi": "10.1371/journal.pmed.1003149", "pmid": "32559194", "labels": {"Affinity Proteomics Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "PMEDICINE-D-20-00136"}, {"db": "pmc", "key": "PMC7304567"}, {"db": "ClinicalTrials.gov", "key": "NCT03814915"}], "notes": [], "created": "2020-12-10T19:03:48.331Z", "modified": "2021-11-10T12:50:35.188Z"}]}