[{"pmid":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","scopus_import":"1","year":"2026","has_accepted_license":"1","tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"title":"Separating direct, indirect, and parent-of-origin genetic effects in the human population","publisher":"Elsevier","dataavailabilitystatement":"Information on how to access the MoBaPsychGen post-imputation QC data are available here: https://www.fhi.no/en/me/the-psychgen-centre-for-genetic-epidemiology-and-mental-health/access-to-genetic-data-after-quality-control-by-the-mobapsychgen-pipeline-v/.\r\nEstonian Biobank data (https://genomics.ut.ee/en/content/estonian-biobank) were used in this project. For access to be granted to the Estonian Biobank genotypic and corresponding phenotypic data, a preliminary application must be presented to the oversight committee, who must first approve the project. Ethics permission must then be obtained from the Estonian Committee on Bioethics and Human Research. Finally, a full project must be submitted and approved by the Estonian Biobank.\r\nAccess to the Generation Scotland data is available with appropriate permission from the Generation Scotland Access Committee. Applications should be made to access@generationscotland.org (https://genscot.ed.ac.uk/).\r\nThe code for JODIE developed in this work is open source and is publicly available on zenodo (https://doi.org/10.5281/zenodo.19593928) and GitHub (https://github.com/medical-genomics-group/JODIE).\r\nHaplotype Reference Consortium Release 1.1 data (https://ega-archive.org/datasets/EGAD00001002729) are available by application to a Data Access Committee (DAC) of the Wellcome Trust Sanger Institute.\r\nThe Common Metabolic Diseases Atlas can be accessed here: https://cmdga.org.","keyword":["direct genetic effects","DGE","indirect genetic effects","IGE","parent-of-origin effects","phenotypic variation","assortative mating","within-family GWAS","MoBa","EstBB"],"abstract":[{"lang":"eng","text":"We introduce JODIE, a genetic joint modeling approach that estimates how DNA loci influence human traits by partitioning genetic effects into four components: direct effects (from a child’s alleles), indirect maternal and paternal effects (from parents’ alleles), and parent-of-origin (PofO) effects (dependent on parental transmission of alleles), while uniquely accounting for assortative mating. We analyze 30,000 child-mother-father trios from the Estonian Biobank and the Norwegian Mother, Father, and Child Cohort, focusing on height, body mass index, and childhood educational test scores. We find direct effects to be the largest contributor to trait variation, but combined, indirect parental and PofO effects are similarly substantial. We support our results by within-family genome-wide association testing and identify 276 independently associated DNA regions with a complex interplay between direct, indirect, and PofO effects. By joint modeling, we show that direct, indirect, and PofO effects collectively shape human phenotypic variation across loci genome-wide."}],"citation":{"short":"I. Krätschmer, L. Hegemann, R.J. Hofmeister, E.C. Corfield, M. Mahmoudi, O. Delaneau, O.A. Andreassen, A. Campbell, C. Hayward, R.E. Marioni, E. Ystrom, A. Havdahl, M.R. Robinson, Cell Genomics 6 (2026).","chicago":"Krätschmer, Ilse, Laura Hegemann, Robin J. Hofmeister, Elizabeth C. Corfield, Mahdi Mahmoudi, Olivier Delaneau, Ole A. Andreassen, et al. “Separating Direct, Indirect, and Parent-of-Origin Genetic Effects in the Human Population.” <i>Cell Genomics</i>. Elsevier, 2026. <a href=\"https://doi.org/10.1016/j.xgen.2026.101277\">https://doi.org/10.1016/j.xgen.2026.101277</a>.","ista":"Krätschmer I, Hegemann L, Hofmeister RJ, Corfield EC, Mahmoudi M, Delaneau O, Andreassen OA, Campbell A, Hayward C, Marioni RE, Ystrom E, Havdahl A, Robinson MR. 2026. Separating direct, indirect, and parent-of-origin genetic effects in the human population. Cell Genomics. 6(7), 101277.","ama":"Krätschmer I, Hegemann L, Hofmeister RJ, et al. Separating direct, indirect, and parent-of-origin genetic effects in the human population. <i>Cell Genomics</i>. 2026;6(7). doi:<a href=\"https://doi.org/10.1016/j.xgen.2026.101277\">10.1016/j.xgen.2026.101277</a>","ieee":"I. Krätschmer <i>et al.</i>, “Separating direct, indirect, and parent-of-origin genetic effects in the human population,” <i>Cell Genomics</i>, vol. 6, no. 7. Elsevier, 2026.","mla":"Krätschmer, Ilse, et al. “Separating Direct, Indirect, and Parent-of-Origin Genetic Effects in the Human Population.” <i>Cell Genomics</i>, vol. 6, no. 7, 101277, Elsevier, 2026, doi:<a href=\"https://doi.org/10.1016/j.xgen.2026.101277\">10.1016/j.xgen.2026.101277</a>.","apa":"Krätschmer, I., Hegemann, L., Hofmeister, R. J., Corfield, E. C., Mahmoudi, M., Delaneau, O., … Robinson, M. R. (2026). Separating direct, indirect, and parent-of-origin genetic effects in the human population. <i>Cell Genomics</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xgen.2026.101277\">https://doi.org/10.1016/j.xgen.2026.101277</a>"},"issue":"7","month":"07","date_created":"2026-06-10T07:39:08Z","project":[{"name":"Improving estimation and prediction of common complex disease risk","grant_number":"PCEGP3_181181","_id":"9B8D11D6-BA93-11EA-9121-9846C619BF3A"}],"das_tickbox":"1","status":"public","doi":"10.1016/j.xgen.2026.101277","OA_place":"publisher","language":[{"iso":"eng"}],"volume":6,"_id":"21987","quality_controlled":"1","article_processing_charge":"Yes","ddc":["570"],"external_id":{"pmid":["40909755"]},"OA_type":"gold","oa":1,"acknowledged_ssus":[{"_id":"ScienComp"}],"publication":"Cell Genomics","date_updated":"2026-07-28T07:27:01Z","acknowledgement":"We thank Zoltan Kutalik, Peter Visscher, and members of the Robinson group at ISTA for their comments, which improved this manuscript. This work was funded by an SNSF Eccellenza Grant to M.R.R. (PCEGP3-181181) and by core funding from the Institute of Science and Technology Austria.\r\nThe Norwegian Mother, Father, and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this on-going cohort study. We thank the Norwegian Institute of Public Health (NIPH) for generating high-quality genomic data. The research is part of the HARVEST collaboration, supported by the Research Council of Norway (#229624). We also thank the NORMENT Center for providing genotype data, funded by the Research Council of Norway (#223273), South East Norway Health Authorities, and Stiftelsen Kristian Gerhard Jebsen, and in collaboration with deCODE Genetics. We further thank the Center for Diabetes Research, the University of Bergen for providing genotype data funded by the ERC AdG project SELECTionPREDISPOSED, Stiftelsen Kristian Gerhard Jebsen, Trond Mohn Foundation, the Research Council of Norway, the Novo Nordisk Foundation, the University of Bergen, and the Western Norway Health Authorities. The MoBa work was performed on the TSD (Tjeneste for Sensitive Data) facilities, owned by the University of Oslo, operated and developed by the TSD service group at the University of Oslo, IT Department (USIT, tsd-drift@usit.uio.no). E.Y. is supported by the European Union (grant numbers 101045526 and 101073237) and the Research Council of Norway (grant numbers 336078, 288083, and 331640).\r\nWe would like to acknowledge the participants and investigators of the Generation Scotland Cohort study. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). Genotyping and methylation typing of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” [STRADL] ref. 104036/Z/14/Z).\r\nWe would like to thank and acknowledge the participants and investigators of the Estonian Biobank (EstBB) study. The research was conducted using the Estonian Center of Genomics/Roadmap II funded by the Estonian Research Council (project number TT17).\r\nNorwegian analyses were performed on resources provided by Sigma2 - the National Infrastructure for High-Performance Computing and Data Storage in Norway. Estonian Data analysis was carried out in the High-Performance Computing Center cloud provided by University of Tartu. Analysis of the Generation Scotland data and the summary statistics obtained from the other analyses was conducted at IST Austria and is supported by the Scientific Service Units (SSU) of IST Austria through resources provided by Scientific Computing (SciComp).","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","researchdata_availability":"yes","author":[{"orcid":"0000-0002-5636-9259","last_name":"Krätschmer","id":"30d4014e-7753-11eb-b44b-db6d61112e73","full_name":"Krätschmer, Ilse","first_name":"Ilse"},{"first_name":"Laura","full_name":"Hegemann, Laura","last_name":"Hegemann"},{"last_name":"Hofmeister","first_name":"Robin J.","full_name":"Hofmeister, Robin J."},{"last_name":"Corfield","full_name":"Corfield, Elizabeth C.","first_name":"Elizabeth C."},{"last_name":"Mahmoudi","full_name":"Mahmoudi, Mahdi","first_name":"Mahdi"},{"last_name":"Delaneau","first_name":"Olivier","full_name":"Delaneau, Olivier"},{"full_name":"Andreassen, Ole A.","first_name":"Ole A.","last_name":"Andreassen"},{"full_name":"Campbell, Archie","first_name":"Archie","last_name":"Campbell"},{"first_name":"Caroline","full_name":"Hayward, Caroline","last_name":"Hayward"},{"last_name":"Marioni","first_name":"Riccardo E.","full_name":"Marioni, Riccardo E."},{"first_name":"Eivind","full_name":"Ystrom, Eivind","last_name":"Ystrom"},{"last_name":"Havdahl","full_name":"Havdahl, Alexandra","first_name":"Alexandra"},{"first_name":"Matthew Richard","full_name":"Robinson, Matthew Richard","orcid":"0000-0001-8982-8813","last_name":"Robinson","id":"E5D42276-F5DA-11E9-8E24-6303E6697425"}],"publication_identifier":{"eissn":["2666-979X"]},"oa_version":"Published Version","article_number":"101277","article_type":"original","supplementarymaterial":"yes","intvolume":"         6","file":[{"date_updated":"2026-07-28T07:24:50Z","relation":"main_file","success":1,"date_created":"2026-07-28T07:24:50Z","file_id":"22597","content_type":"application/pdf","checksum":"f896b510480d2d4e4a7fd46c2e2761f4","creator":"dernst","file_name":"2026_CellGenomics_Kraetschmer.pdf","file_size":3679297,"access_level":"open_access"}],"publication_status":"published","DOAJ_listed":"1","date_published":"2026-07-08T00:00:00Z","type":"journal_article","department":[{"_id":"MaRo"}],"file_date_updated":"2026-07-28T07:24:50Z","day":"08"},{"has_accepted_license":"1","year":"2016","date_updated":"2026-04-09T10:52:06Z","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"1398"}]},"oa_version":"Published Version","abstract":[{"text":"Genotypic, phenotypic and demographic data for 2128 wild snapdragons and 1127 open-pollinated progeny from a natural hybrid zone, collected as part of Tom Ellis' PhD thesis (submitted) February 2016).\r\n\r\nTissue samples were sent to LGC Genomics in Berlin for DNA extraction, and genotyping at 70 SNP markers by KASPR genotyping. 29 of these SNPs failed to amplify reliably, and have been removed from this dataset.\r\n\r\nOther data were retreived from an online database of this population at www.antspec.org.","lang":"eng"}],"keyword":["paternity assignment","pedigree","matting patterns","assortative mating","Antirrhinum majus","frequency-dependent selection","plant-pollinator interaction"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","image":"/images/cc_0.png","short":"CC0 (1.0)","name":"Creative Commons Public Domain Dedication (CC0 1.0)"},"title":"Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012","author":[{"first_name":"David","full_name":"Field, David","id":"419049E2-F248-11E8-B48F-1D18A9856A87","last_name":"Field","orcid":"0000-0002-4014-8478"},{"orcid":"0000-0002-8511-0254","last_name":"Ellis","id":"3153D6D4-F248-11E8-B48F-1D18A9856A87","full_name":"Ellis, Thomas","first_name":"Thomas"}],"publisher":"Institute of Science and Technology Austria","doi":"10.15479/AT:ISTA:37","file":[{"date_created":"2018-12-12T13:03:02Z","date_updated":"2020-07-14T12:47:01Z","relation":"main_file","file_name":"IST-2016-37-v1+1_paternity_archive.zip","access_level":"open_access","file_size":132808,"content_type":"application/zip","file_id":"5620","checksum":"4ae751b1fa4897fa216241f975a57313","creator":"system"}],"month":"02","citation":{"short":"D. Field, T. Ellis, (2016).","ista":"Field D, Ellis T. 2016. Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:37\">10.15479/AT:ISTA:37</a>.","chicago":"Field, David, and Thomas Ellis. “Inference of Mating Patterns among Wild Snapdragons in a Natural Hybrid Zone in 2012.” Institute of Science and Technology Austria, 2016. <a href=\"https://doi.org/10.15479/AT:ISTA:37\">https://doi.org/10.15479/AT:ISTA:37</a>.","ama":"Field D, Ellis T. Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012. 2016. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:37\">10.15479/AT:ISTA:37</a>","ieee":"D. Field and T. Ellis, “Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012.” Institute of Science and Technology Austria, 2016.","mla":"Field, David, and Thomas Ellis. <i>Inference of Mating Patterns among Wild Snapdragons in a Natural Hybrid Zone in 2012</i>. Institute of Science and Technology Austria, 2016, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:37\">10.15479/AT:ISTA:37</a>.","apa":"Field, D., &#38; Ellis, T. (2016). Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:37\">https://doi.org/10.15479/AT:ISTA:37</a>"},"status":"public","datarep_id":"37","date_created":"2018-12-12T12:31:30Z","department":[{"_id":"NiBa"}],"type":"research_data","day":"19","file_date_updated":"2020-07-14T12:47:01Z","oa":1,"contributor":[{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton","orcid":"0000-0002-8548-5240","first_name":"Nicholas H","contributor_type":"project_manager"}],"_id":"5553","article_processing_charge":"No","date_published":"2016-02-19T00:00:00Z","ddc":["576"]}]