{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:55:01Z","timestamp":1790870101427,"version":"4.1.0"},"reference-count":41,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM161534"],"award-info":[{"award-number":["R35GM161534"]}],"id":[{"id":"10.13039\/100000057","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":[[2026,10]]},"DOI":"10.1016\/j.ajhg.2026.09.003","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:00:26Z","timestamp":1790089226000},"page":"2068-2081","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Robust cis-by-trans epistasis in the human plasma proteome highlights an ABO-centered interaction network"],"prefix":"10.1016","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4854-2613","authenticated-orcid":false,"given":"Jinghui","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5955-6738","authenticated-orcid":false,"given":"Xuanyao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajhg.2026.09.003_bib1","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/ng1986","article-title":"Epistatic buffering of fitness loss in yeast double deletion strains","volume":"39","author":"Jasnos","year":"2007","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib2","doi-asserted-by":"crossref","first-page":"15553","DOI":"10.1073\/pnas.1213423109","article-title":"Epistasis dominates the genetic architecture of Drosophila quantitative traits","volume":"109","author":"Huang","year":"2012","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.ajhg.2026.09.003_bib3","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.35471","article-title":"Genetics of trans-regulatory variation in gene expression","volume":"7","author":"Albert","year":"2018","journal-title":"eLife"},{"key":"10.1016\/j.ajhg.2026.09.003_bib4","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1038\/s41588-025-02411-y","article-title":"A biobank-scale test of marginal epistasis reveals genome-wide signals of polygenic interaction effects","volume":"57","author":"Fu","year":"2025","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib5","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1111\/mec.14051","article-title":"Genetic architecture and balancing selection: the life and death of differentiated variants","volume":"26","author":"Llaurens","year":"2017","journal-title":"Mol. Ecol."},{"key":"10.1016\/j.ajhg.2026.09.003_bib6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nature03480","article-title":"Epistasis and balanced polymorphism influencing complex trait variation","volume":"435","author":"Kroymann","year":"2005","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2026.09.003_bib7","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nrg3747","article-title":"Detecting epistasis in human complex traits","volume":"15","author":"Wei","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib8","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.ajhg.2021.02.014","article-title":"Estimation of non-additive genetic variance in human complex traits from a large sample of unrelated individuals","volume":"108","author":"Hivert","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib9","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/ng.3162","article-title":"Gene-gene and gene-environment interactions detected by transcriptome sequence analysis in twins","volume":"47","author":"Buil","year":"2015","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib10","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41467-019-13762-6","article-title":"Using regulatory variants to detect gene\u2013gene interactions identifies networks of genes linked to cell immortalisation","volume":"11","author":"Wragg","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2026.09.003_bib11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1009719","article-title":"Transcription factor regulation of eQTL activity across individuals and tissues","volume":"18","author":"Flynn","year":"2022","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib12","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.ajhg.2025.01.015","article-title":"reg-eQTL: Integrating transcription factor effects to unveil regulatory variants","volume":"112","author":"Mudappathi","year":"2025","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib13","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","article-title":"Plasma proteomic associations with genetics and health in the UK Biobank","volume":"622","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2026.09.003_bib14","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41467-025-67235-0","article-title":"Complex genetic effects linked to plasma protein abundance in the UK Biobank","volume":"17","author":"Sigurdsson","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2026.09.003_bib15","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1038\/s41586-021-03765-z","article-title":"Phantom epistasis between unlinked loci","volume":"596","author":"Hemani","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2026.09.003_bib16","article-title":"Characterizing the genetic architecture of drug response using gene-context interaction methods","volume":"4","author":"Sadowski","year":"2024","journal-title":"Cell Genom."},{"key":"10.1016\/j.ajhg.2026.09.003_bib17","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/ng.3506","article-title":"Integrative approaches for large-scale transcriptome-wide association studies","volume":"48","author":"Gusev","year":"2016","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib18","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","article-title":"GCTA: A Tool for Genome-wide Complex Trait Analysis","volume":"88","author":"Yang","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v095.i01","article-title":"Various Versatile Variances: An Object-Oriented Implementation of Clustered Covariances in R","volume":"95","author":"Zeileis","year":"2020","journal-title":"J. Stat. Softw."},{"key":"10.1016\/j.ajhg.2026.09.003_bib20","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genomewide studies","volume":"100","author":"Storey","year":"2003","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.ajhg.2026.09.003_bib21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nature14248","article-title":"Integrative analysis of 111 reference human epigenomes","volume":"518","author":"Kundaje","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2026.09.003_bib22","doi-asserted-by":"crossref","unstructured":"Canty, A., and Ripley, B. boot: Bootstrap Functions , https:\/\/doi.org\/10.32614\/CRAN.package.boot (1999).","DOI":"10.32614\/CRAN.package.boot"},{"key":"10.1016\/j.ajhg.2026.09.003_bib23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41588-025-02449-y","article-title":"Protein\u2013protein interactions shape trans-regulatory impact of genetic variation on protein expression and complex traits","volume":"58","author":"Li","year":"2026","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib24","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1101\/gr.4326505","article-title":"Genomic regions exhibiting positive selection identified from dense genotype data","volume":"15","author":"Carlson","year":"2005","journal-title":"Genome Res."},{"key":"10.1016\/j.ajhg.2026.09.003_bib25","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/ng.3367","article-title":"A gene-based association method for mapping traits using reference transcriptome data","volume":"47","author":"Gamazon","year":"2015","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib26","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1038\/nprot.2017.124","article-title":"Chromatin-state discovery and genome annotation with ChromHMM","volume":"12","author":"Ernst","year":"2017","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.ajhg.2026.09.003_bib27","article-title":"Positional distribution of transcription factor binding sites in the human genome","volume":"20","author":"Yu","year":"2025","journal-title":"PLoS One"},{"key":"10.1016\/j.ajhg.2026.09.003_bib28","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1001\/jamapsychiatry.2025.0033","article-title":"Circulating Blood-Based Proteins in Psychopathology and Cognition: A Mendelian Randomization Study","volume":"82","author":"Bhattacharyya","year":"2025","journal-title":"JAMA Psychiatry"},{"key":"10.1016\/j.ajhg.2026.09.003_bib29","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ajhg.2024.12.010","article-title":"Multivariate proteome-wide association study to identify causal proteins for Alzheimer disease","volume":"112","author":"Fang","year":"2025","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib30","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1038\/s41467-025-56695-z","article-title":"Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities","volume":"16","author":"Loesch","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2026.09.003_bib31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000072","article-title":"A Genome-Wide Association Study Identifies Protein Quantitative Trait Loci (pQTLs)","volume":"4","author":"Melzer","year":"2008","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00439-008-0530-8","article-title":"Evolutionary dynamics of the human ABO gene","volume":"124","author":"Calafell","year":"2008","journal-title":"Hum. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib33","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/j.1423-0410.2009.01291.x","article-title":"Distribution of ABO blood group allele and identification of three novel alleles in the Chinese Han population","volume":"98","author":"Zhu","year":"2010","journal-title":"Vox Sang."},{"key":"10.1016\/j.ajhg.2026.09.003_bib34","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ejmhg.2014.09.002","article-title":"Frequency distribution of ABO and Rh (D) blood group alleles in Silte Zone, Ethiopia","volume":"16","author":"Tesfaye","year":"2015","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib35","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1186\/s12864-016-2687-1","article-title":"ABO allele-level frequency estimation based on population-scale genotyping by next generation sequencing","volume":"17","author":"Lang","year":"2016","journal-title":"BMC Genom."},{"key":"10.1016\/j.ajhg.2026.09.003_bib36","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1093\/hmg\/ddl193","article-title":"Evolutionary insights into the high worldwide prevalence of MBL2 deficiency alleles","volume":"15","author":"Verdu","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2026.09.003_bib37","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1016\/j.molimm.2009.05.005","article-title":"MBL2, FCN1, FCN2 and FCN3\u2014The genes behind the initiation of the lectin pathway of complement","volume":"46","author":"Garred","year":"2009","journal-title":"Mol. Immunol."},{"key":"10.1016\/j.ajhg.2026.09.003_bib38","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/imr.12341","article-title":"Fc\u03b3 receptors: genetic variation, function, and disease","volume":"268","author":"Hargreaves","year":"2015","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.ajhg.2026.09.003_bib39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/biology10010001","article-title":"C-type Lectin CD209L\/L-SIGN and CD209\/DC-SIGN: Cell Adhesion Molecules Turned to Pathogen Recognition Receptors","volume":"10","author":"Rahimi","year":"2020","journal-title":"Biology"},{"key":"10.1016\/j.ajhg.2026.09.003_bib40","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1038\/s41467-026-69152-2","article-title":"Protein-protein interactions are a major source of epistasis in genetic interaction networks","volume":"17","author":"Castellanos-Girouard","year":"2026","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2026.09.003_bib41","doi-asserted-by":"crossref","first-page":"5122","DOI":"10.1038\/s41467-025-60056-1","article-title":"Performance of deep-learning-based approaches to improve polygenic scores","volume":"16","author":"Kelemen","year":"2025","journal-title":"Nat. Commun."}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929726003447?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929726003447?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:02:50Z","timestamp":1790866970000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929726003447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":41,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["S0002929726003447"],"URL":"https:\/\/doi.org\/10.1016\/j.ajhg.2026.09.003","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Robust cis-by-trans epistasis in the human plasma proteome highlights an ABO-centered interaction network","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.2026.09.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc. on behalf of American Society of Human Genetics.","name":"copyright","label":"Copyright"}]}}