{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:29:32Z","timestamp":1786984172308,"version":"build-2736575974"},"reference-count":85,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T00:00:00Z","timestamp":1591315200000},"content-version":"vor","delay-in-days":187,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT107881"],"award-info":[{"award-number":["WT107881"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004325","name":"Signe ja Ane Gyllenbergin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003125","name":"Suomen Kulttuurirahasto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011797","name":"Turun Yliopistollinen Keskussairaala","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011797","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006706","name":"Tampereen Tuberkuloosis\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006706","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008484","name":"Paavo Nurmen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008484","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1090462"],"award-info":[{"award-number":["1090462"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["742927"],"award-info":[{"award-number":["742927"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["312476"],"award-info":[{"award-number":["312476"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["15998"],"award-info":[{"award-number":["15998"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["321356"],"award-info":[{"award-number":["321356"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["312477"],"award-info":[{"award-number":["312477"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF17OC0026062"],"award-info":[{"award-number":["NNF17OC0026062"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/13\/13\/30194"],"award-info":[{"award-number":["RG\/13\/13\/30194"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/18\/13\/33946"],"award-info":[{"award-number":["RG\/18\/13\/33946"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004037","name":"Juho Vainion S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004037","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004756","name":"Emil Aaltosen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004756","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["755320"],"award-info":[{"award-number":["755320"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008415","name":"Diabetesliitto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005633","name":"Syd\u00e4ntutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010600","name":"Tays","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010600","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010114","name":"Yrj\u00f6 Jahnssonin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010114","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012141","name":"University Hospitals Bristol NHS Foundation Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["124282"],"award-info":[{"award-number":["124282"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["286284"],"award-info":[{"award-number":["286284"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["121584"],"award-info":[{"award-number":["121584"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["322098"],"award-info":[{"award-number":["322098"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["126925"],"award-info":[{"award-number":["126925"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["117787"],"award-info":[{"award-number":["117787"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["41071"],"award-info":[{"award-number":["41071"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["134309"],"award-info":[{"award-number":["134309"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["129378"],"award-info":[{"award-number":["129378"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004752","name":"State Government of Victoria","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004752","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L003120\/1"],"award-info":[{"award-number":["MR\/L003120\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00002\/4"],"award-info":[{"award-number":["MC_UU_00002\/4"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["297338"],"award-info":[{"award-number":["297338"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["307247"],"award-info":[{"award-number":["307247"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1016\/j.ajhg.2019.10.001","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T21:35:21Z","timestamp":1572557721000},"page":"1076-1090","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":42,"title":["Multivariate Genome-wide Association Analysis of a Cytokine Network Reveals Variants with Widespread Immune, Haematological, and Cardiometabolic Pleiotropy"],"prefix":"10.1016","volume":"105","author":[{"given":"Artika P.","family":"Nath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Ritchie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nastasiya F.","family":"Grinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard Ho-Fung","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin Qin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu Mei","family":"Teo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari V.","family":"Ahola-Olli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"W\u00fcrtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki S.","family":"Havulinna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristiina","family":"Santalahti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niina","family":"Pitk\u00e4nen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terho","family":"Lehtim\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"K\u00e4h\u00f6nen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo-Pekka","family":"Lyytik\u00e4inen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Raitoharju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Sepp\u00e4l\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti-Pekka","family":"Sarin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuli","family":"Ripatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarno","family":"Palotie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Perola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorma S.","family":"Viikari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirpa","family":"Jalkanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Maksimow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Salmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli T.","family":"Raitakari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veikko","family":"Salomaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gad","family":"Abraham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kettunen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Inouye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Suppl 1","key":"10.1016\/j.ajhg.2019.10.001_bib1","doi-asserted-by":"crossref","first-page":"S34","DOI":"10.1002\/eji.200737772","article-title":"Historical insights into cytokines","volume":"37","author":"Dinarello","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib2","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/ni.2366","article-title":"IL-12 family cytokines: immunological playmakers","volume":"13","author":"Vignali","year":"2012","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib3","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nri702","article-title":"Cytokines and autoimmunity","volume":"2","author":"O\u2019Shea","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc1252","article-title":"Cytokines in cancer pathogenesis and cancer therapy","volume":"4","author":"Dranoff","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ajhg.2019.10.001_bib5","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1161\/ATVBAHA.110.207415","article-title":"Recent advances on the role of cytokines in atherosclerosis","volume":"31","author":"Dranoff","year":"2011","journal-title":"Arterioscler Thromb. Vasc. Biol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib6","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1093\/eurheartj\/eht367","article-title":"Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis","volume":"35","author":"Kaptoge","year":"2014","journal-title":"Eur. Heart J."},{"key":"10.1016\/j.ajhg.2019.10.001_bib7","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/sj.gene.6364162","article-title":"Heritability estimates of innate immunity: an extended twin study","volume":"6","author":"de Craen","year":"2005","journal-title":"Genes Immun."},{"key":"10.1016\/j.ajhg.2019.10.001_bib8","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/sj.gene.6364393","article-title":"Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels","volume":"8","author":"Rafiq","year":"2007","journal-title":"Genes Immun."},{"key":"10.1016\/j.ajhg.2019.10.001_bib9","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S2213-8587(15)00034-0","article-title":"Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis","volume":"3","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib10","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/sj.gene.6364301","article-title":"Cytokine gene polymorphism in human disease: on-line databases, Supplement 3","volume":"7","author":"Hollegaard","year":"2006","journal-title":"Genes Immun."},{"key":"10.1016\/j.ajhg.2019.10.001_bib11","doi-asserted-by":"crossref","first-page":"e66262","DOI":"10.1371\/journal.pone.0066262","article-title":"Genome-wide association study of genetic variants in LPS-stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-\u03b1 cytokine response in a Danish cohort","volume":"8","author":"Larsen","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ajhg.2019.10.001_bib12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cyto.2013.10.002","article-title":"Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults","volume":"65","author":"Matteini","year":"2014","journal-title":"Cytokine"},{"key":"10.1016\/j.ajhg.2019.10.001_bib13","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00251-011-0596-7","article-title":"Genome-wide associated loci influencing interleukin (IL)-10, IL-1Ra, and IL-6 levels in African Americans","volume":"64","author":"Tekola Ayele","year":"2012","journal-title":"Immunogenetics"},{"key":"10.1016\/j.ajhg.2019.10.001_bib14","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1161\/CIRCRESAHA.111.243790","article-title":"Identification of cis- and trans-acting genetic variants explaining up to half the variation in circulating vascular endothelial growth factor levels","volume":"109","author":"Debette","year":"2011","journal-title":"Circ. Res."},{"key":"10.1016\/j.ajhg.2019.10.001_bib15","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1161\/ATVBAHA.109.199422","article-title":"Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels","volume":"30","author":"He","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib16","doi-asserted-by":"crossref","first-page":"e1005874","DOI":"10.1371\/journal.pgen.1005874","article-title":"Six novel loci associated with circulating VEGF levels identified by a meta-analysis of genome-wide association studies","volume":"12","author":"Choi","year":"2016","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41586-018-0175-2","article-title":"Genomic atlas of the human plasma proteome","volume":"558","author":"Sun","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2019.10.001_bib18","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1136\/jmedgenet-2018-105965","article-title":"Genome-wide association study identifies seven novel loci associating with circulating cytokines and\u00a0cell adhesion molecules in Finns","volume":"56","author":"Sliz","year":"2019","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib19","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ajhg.2016.11.007","article-title":"Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors","volume":"100","author":"Ahola-Olli","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib20","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/nm.4139","article-title":"Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi","volume":"22","author":"Li","year":"2016","journal-title":"Nat. Med."},{"key":"10.1016\/j.ajhg.2019.10.001_bib21","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.cell.2016.10.017","article-title":"A functional genomics approach to understand variation in cytokine production in humans","volume":"167","author":"Li","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2019.10.001_bib22","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1093\/bioinformatics\/btn563","article-title":"A multivariate test of association","volume":"25","author":"Ferreira","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ajhg.2019.10.001_bib23","doi-asserted-by":"crossref","first-page":"e34861","DOI":"10.1371\/journal.pone.0034861","article-title":"MultiPhen: joint model of multiple phenotypes can increase discovery in GWAS","volume":"7","author":"O\u2019Reilly","year":"2012","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ajhg.2019.10.001_bib24","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nmeth.2848","article-title":"Efficient multivariate linear mixed model algorithms for genome-wide association studies","volume":"11","author":"Zhou","year":"2014","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ajhg.2019.10.001_bib25","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41588-017-0009-4","article-title":"Multi-trait analysis of genome-wide association summary statistics using MTAG","volume":"50","author":"Turley","year":"2018","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib26","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1093\/bioinformatics\/btw052","article-title":"metaCCA: summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis","volume":"32","author":"Cichonska","year":"2016","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ajhg.2019.10.001_bib27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12859-016-1437-3","article-title":"SCOPA and META-SCOPA: software for the analysis and aggregation of genome-wide association studies of multiple correlated phenotypes","volume":"18","author":"M\u00e4gi","year":"2017","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.ajhg.2019.10.001_bib28","first-page":"652569","article-title":"Methods for analyzing multivariate phenotypes in genetic association studies","volume":"2012","author":"Yang","year":"2012","journal-title":"J.\u00a0Probab. Stat."},{"key":"10.1016\/j.ajhg.2019.10.001_bib29","doi-asserted-by":"crossref","first-page":"e1000587","DOI":"10.1371\/journal.pgen.1000587","article-title":"Statistical estimation of correlated genome associations to a quantitative trait network","volume":"5","author":"Kim","year":"2009","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib30","doi-asserted-by":"crossref","first-page":"e1003235","DOI":"10.1371\/journal.pgen.1003235","article-title":"TATES: efficient multivariate genotype-phenotype analysis for genome-wide association studies","volume":"9","author":"van der Sluis","year":"2013","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib31","doi-asserted-by":"crossref","first-page":"e1002907","DOI":"10.1371\/journal.pgen.1002907","article-title":"Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis","volume":"8","author":"Inouye","year":"2012","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib32","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1093\/bioinformatics\/btu140","article-title":"Assessing multivariate gene-metabolome associations with rare variants using Bayesian reduced rank regression","volume":"30","author":"Marttinen","year":"2014","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ajhg.2019.10.001_bib33","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1093\/ije\/dym225","article-title":"Cohort profile: the cardiovascular risk in Young Finns Study","volume":"37","author":"Raitakari","year":"2008","journal-title":"Int. J. Epidemiol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib34","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/eurpub\/cku174","article-title":"Forty-year trends in cardiovascular risk factors in Finland","volume":"25","author":"Borodulin","year":"2015","journal-title":"Eur. J. Public Health"},{"key":"10.1016\/j.ajhg.2019.10.001_bib35","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1093\/bioinformatics\/btm443","article-title":"A genotype calling algorithm for the Illumina BeadArray platform","volume":"23","author":"Teo","year":"2007","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ajhg.2019.10.001_bib36","doi-asserted-by":"crossref","first-page":"e1000529","DOI":"10.1371\/journal.pgen.1000529","article-title":"A flexible and accurate genotype imputation method for the next generation of genome-wide association studies","volume":"5","author":"Howie","year":"2009","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib37","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":"10.1016\/j.ajhg.2019.10.001_bib38","doi-asserted-by":"crossref","first-page":"e93766","DOI":"10.1371\/journal.pone.0093766","article-title":"Fast principal component analysis of large-scale genome-wide data","volume":"9","author":"Abraham","year":"2014","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ajhg.2019.10.001_bib39","first-page":"1","article-title":"missMDA: A package for handling missing values in multivariate data analysis","volume":"70","author":"Josse","year":"2016","journal-title":"J.\u00a0Stat. Softw."},{"key":"10.1016\/j.ajhg.2019.10.001_bib40","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1111\/j.1365-3016.2008.00969.x","article-title":"Assays with lower detection limits: implications for epidemiological investigations","volume":"22","author":"Whitcomb","year":"2008","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib41","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1093\/bioinformatics\/btm108","article-title":"GenABEL: an R library for genome-wide association analysis","volume":"23","author":"Aulchenko","year":"2007","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ajhg.2019.10.001_bib42","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":"10.1016\/j.ajhg.2019.10.001_bib43","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1111\/j.1420-9101.2005.00917.x","article-title":"Combining probability from independent tests: the weighted Z-method is superior to Fisher\u2019s approach","volume":"18","author":"Whitlock","year":"2005","journal-title":"J.\u00a0Evol. Biol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib44","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1111\/j.1420-9101.2011.02297.x","article-title":"Optimally weighted Z-test is a powerful method for combining probabilities in meta-analysis","volume":"24","author":"Zaykin","year":"2011","journal-title":"J.\u00a0Evol. Biol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib45","doi-asserted-by":"crossref","first-page":"e1004383","DOI":"10.1371\/journal.pgen.1004383","article-title":"Bayesian test for colocalisation between pairs of genetic association studies using summary statistics","volume":"10","author":"Giambartolomei","year":"2014","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib46","article-title":"Unraveling the polygenic architecture of complex traits using blood eQTL meta-analysis","volume":"447367","author":"V\u00f5sa","year":"2018","journal-title":"bioRxiv"},{"key":"10.1016\/j.ajhg.2019.10.001_bib47","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/ng.2205","article-title":"Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles","volume":"44","author":"Fairfax","year":"2012","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib48","doi-asserted-by":"crossref","first-page":"1246949","DOI":"10.1126\/science.1246949","article-title":"Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression","volume":"343","author":"Fairfax","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.ajhg.2019.10.001_bib49","doi-asserted-by":"crossref","first-page":"e1006643","DOI":"10.1371\/journal.pgen.1006643","article-title":"Pathogenic implications for autoimmune mechanisms derived by comparative eQTL analysis of CD4+ versus CD8+ T\u00a0cells","volume":"13","author":"Kasela","year":"2017","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib50","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1093\/hmg\/ddv077","article-title":"Integration of disease association and eQTL data using a Bayesian colocalisation approach highlights six candidate causal genes in immune-mediated diseases","volume":"24","author":"Guo","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib51","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1093\/bioinformatics\/bty147","article-title":"A Bayesian framework for multiple trait colocalization from summary association statistics","volume":"34","author":"Giambartolomei","year":"2018","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ajhg.2019.10.001_bib52","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/cr.2009.138","article-title":"Heterogeneity and plasticity of T helper cells","volume":"20","author":"Zhu","year":"2010","journal-title":"Cell Res."},{"key":"10.1016\/j.ajhg.2019.10.001_bib53","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nri2295","article-title":"TH17 cells in development: an updated view of their molecular identity and genetic programming","volume":"8","author":"Dong","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib54","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/wrr.12205","article-title":"Clinical application of growth factors and cytokines in wound healing","volume":"22","author":"Barrientos","year":"2014","journal-title":"Wound Repair Regen."},{"key":"10.1016\/j.ajhg.2019.10.001_bib55","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.immuni.2009.09.002","article-title":"Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases","volume":"31","author":"Hu","year":"2009","journal-title":"Immunity"},{"key":"10.1016\/j.ajhg.2019.10.001_bib56","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1182\/blood-2011-10-387167","article-title":"Expression of ABO blood-group genes is dependent upon an erythroid cell-specific regulatory element that is deleted in persons with the B(m) phenotype","volume":"119","author":"Sano","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.ajhg.2019.10.001_bib57","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.cell.2016.10.026","article-title":"Genetic drivers of epigenetic and transcriptional variation in human immune cells","volume":"167","author":"Chen","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2019.10.001_bib58","doi-asserted-by":"crossref","first-page":"D1001","DOI":"10.1093\/nar\/gkt1229","article-title":"The NHGRI GWAS Catalog, a curated resource of SNP-trait associations","volume":"42","author":"Welter","year":"2014","journal-title":"Nucleic Acids Res."},{"issue":"D1","key":"10.1016\/j.ajhg.2019.10.001_bib59","doi-asserted-by":"crossref","first-page":"D896","DOI":"10.1093\/nar\/gkw1133","article-title":"The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog)","volume":"45","author":"MacArthur","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2019.10.001_bib60","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.cell.2016.10.042","article-title":"The allelic landscape of human blood cell trait variation and links to common complex disease","volume":"167","author":"Astle","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2019.10.001_bib61","doi-asserted-by":"crossref","first-page":"e95923","DOI":"10.1371\/journal.pone.0095923","article-title":"A comparison of multivariate genome-wide association methods","volume":"9","author":"Galesloot","year":"2014","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ajhg.2019.10.001_bib62","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1182\/blood-2011-10-387464","article-title":"Emerging role of serpinE2\/protease nexin-1 in hemostasis and vascular biology","volume":"119","author":"Bouton","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.ajhg.2019.10.001_bib63","doi-asserted-by":"crossref","first-page":"e0135979","DOI":"10.1371\/journal.pone.0135979","article-title":"SERPINE2 inhibits IL-1\u03b1-induced MMP-13 expression in human chondrocytes: Involvement of ERK\/NF-\u03baB\/AP-1 pathways","volume":"10","author":"Santoro","year":"2015","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ajhg.2019.10.001_bib64","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1096\/fj.201500159R","article-title":"Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation","volume":"30","author":"Solleti","year":"2016","journal-title":"FASEB J."},{"key":"10.1016\/j.ajhg.2019.10.001_bib65","doi-asserted-by":"crossref","first-page":"6601","DOI":"10.1038\/srep06601","article-title":"An integrative evolution theory of histo-blood group ABO and related genes","volume":"4","author":"Yamamoto","year":"2014","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ajhg.2019.10.001_bib66","doi-asserted-by":"crossref","first-page":"e0142518","DOI":"10.1371\/journal.pone.0142518","article-title":"Genome-wide association study identifies that the ABO blood group system influences interleukin-10 levels and the risk of clinical events in patients with acute coronary syndrome","volume":"10","author":"Johansson","year":"2015","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ajhg.2019.10.001_bib67","doi-asserted-by":"crossref","first-page":"15019","DOI":"10.1038\/hgv.2015.19","article-title":"Interaction of genetic markers associated with serum alkaline phosphatase levels in the Japanese population","volume":"2","author":"Masuda","year":"2015","journal-title":"Hum. Genome Var."},{"key":"10.1016\/j.ajhg.2019.10.001_bib68","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1038\/s41467-018-05512-x","article-title":"Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease","volume":"9","author":"Yao","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2019.10.001_bib69","first-page":"237","article-title":"Association of ABO and Rh blood groups with type 2 diabetes mellitus","volume":"20","author":"Meo","year":"2016","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"10.1016\/j.ajhg.2019.10.001_bib70","doi-asserted-by":"crossref","first-page":"23250","DOI":"10.1038\/srep23250","article-title":"ABO blood group system and the coronary artery disease: an updated systematic review and meta-analysis","volume":"6","author":"Chen","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ajhg.2019.10.001_bib71","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.atherosclerosis.2016.05.049","article-title":"ABO blood group associations with markers of endothelial dysfunction in the Multi-Ethnic Study of Atherosclerosis","volume":"251","author":"Larson","year":"2016","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.ajhg.2019.10.001_bib72","doi-asserted-by":"crossref","first-page":"e1000118","DOI":"10.1371\/journal.pgen.1000118","article-title":"Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women","volume":"4","author":"Par\u00e9","year":"2008","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib73","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1093\/hmg\/ddq057","article-title":"Genetic variants in ABO blood group region, plasma soluble E-selectin levels and risk of type 2 diabetes","volume":"19","author":"Qi","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2019.10.001_bib74","doi-asserted-by":"crossref","first-page":"14357","DOI":"10.1038\/ncomms14357","article-title":"Connecting genetic risk to disease end points through the human blood plasma proteome","volume":"8","author":"Suhre","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2019.10.001_bib75","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s00125-014-3472-9","article-title":"ABO and Rhesus blood groups and risk of type 2 diabetes: evidence from the large E3N cohort study","volume":"58","author":"Fagherazzi","year":"2015","journal-title":"Diabetologia"},{"key":"10.1016\/j.ajhg.2019.10.001_bib76","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1161\/hq0202.103997","article-title":"Amount of H antigen expressed on circulating von Willebrand factor is modified by ABO blood group genotype and is a major determinant of plasma von Willebrand factor antigen levels","volume":"22","author":"O\u2019Donnell","year":"2002","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib77","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1160\/TH04-04-0251","article-title":"The ABO blood group genotype and factor VIII levels as independent risk factors for venous thromboembolism","volume":"93","author":"Tirado","year":"2005","journal-title":"Thromb. Haemost."},{"key":"10.1016\/j.ajhg.2019.10.001_bib78","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/j.1365-2141.2004.05249.x","article-title":"Relationship between ABO and Secretor genotype with plasma levels of factor VIII and von Willebrand factor in thrombosis patients and control individuals","volume":"128","author":"Schleef","year":"2005","journal-title":"Br. J. Haematol."},{"key":"10.1016\/j.ajhg.2019.10.001_bib79","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1073\/pnas.96.3.956","article-title":"Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in cardiomyocytes","volume":"96","author":"Svensson","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2019.10.001_bib80","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1172\/JCI32573","article-title":"Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart","volume":"117","author":"Heineke","year":"2007","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.ajhg.2019.10.001_bib81","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1172\/JCI38723","article-title":"Fog2 is critical for cardiac function and maintenance of coronary vasculature in the adult mouse heart","volume":"119","author":"Zhou","year":"2009","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.ajhg.2019.10.001_bib82","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41426-018-0090-5","article-title":"Relationship between circulating vascular endothelial growth factor and its soluble receptor in patients with hemorrhagic fever with renal syndrome","volume":"7","author":"Pal","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"10.1016\/j.ajhg.2019.10.001_bib83","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1038\/bjc.1998.158","article-title":"Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology","volume":"77","author":"Banks","year":"1998","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.ajhg.2019.10.001_bib84","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1124\/jpet.300.3.952","article-title":"Close relationship between the platelet activation marker CD62 and the granular release of platelet-derived growth factor","volume":"300","author":"Graff","year":"2002","journal-title":"J.\u00a0Pharmacol. Exp. Ther."},{"key":"10.1016\/j.ajhg.2019.10.001_bib85","doi-asserted-by":"crossref","first-page":"D204","DOI":"10.1093\/nar\/gku989","article-title":"UniProt: a hub for protein information","volume":"43","year":"2015","journal-title":"Nucleic Acids Res."}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929719303891?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929719303891?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:44:49Z","timestamp":1777376689000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929719303891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":85,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["S0002929719303891"],"URL":"https:\/\/doi.org\/10.1016\/j.ajhg.2019.10.001","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/544445","asserted-by":"object"}]},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Multivariate Genome-wide Association Analysis of a Cytokine Network Reveals Variants with Widespread Immune, Haematological, and Cardiometabolic Pleiotropy","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Human Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajhg.2019.10.001","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 American Society of Human Genetics.","name":"copyright","label":"Copyright"}]}}