ArticleNature communications2023
Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality.
Erratum issuedOpen access · goldAbstract read
In one paragraph
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 6% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Meta-analysis across six global biobanks identifies recessive coding associations with complex traits and diseases.American journal of human genetics · 2026Pooled it
- Assessing Hardy-Weinberg equilibrium in T2T-aligned 1000 genomes project.PLoS genetics · 2026Article
- Genomics of pregnancy loss.Journal of assisted reproduction and genetics · 2026Review
- GREGoR: accelerating genomics for rare diseases.Nature · 2025Article
- Article
- Sequence diversity lost in early pregnancy.Nature · 2025Article
- Bi-allelic variants in BRF2 are associated with perinatal death and craniofacial anomalies.Genome medicine · 2025Article
- The effects of runs-of-homozygosity on pig domestication and breeding.BMC genomics · 2025Article
- Lethal phenotypes in Mendelian disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination.Nature structural & molecular biology · 2024Article
- High Incidence ofBalkan medical journal · 2024Article
- Goldilocks principle and recessive disease.European journal of human genetics : EJHG · 2024Article
- Lethal phenotypes in Mendelian disorders.medRxiv : the preprint server for health sciences · 2024Article
- The dopamine hypothesis for ADHD: An evaluation of evidence accumulated from human studies and animal models.Frontiers in psychiatry · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
76 authors at 20 institutions in 6 countries.
Asmundur Oddsson *deCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0002-4606-5163
Patrick Sulem *deCODE genetics/Amgen, Inc., Reykjavik, Iceland. patrick.sulem@decode.is.ORCID 0000-0001-7123-6123
Gardar SveinbjornssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0003-2429-9468
Gudny A ArnadottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0001-6571-423X
Valgerdur SteinthorsdottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0003-1846-6274
Gisli H HalldorssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0001-7067-9862
Bjarni A AtlasondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0001-6316-5812
Gudjon R OskarssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0002-1842-8799
Hannes HelgasondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Henriette Svarre NielsenDeptartment of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre, Denmark.ORCID 0000-0003-2106-8103
David WestergaardDeptartment of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre, Denmark.ORCID 0000-0003-0128-8432
Juha M KarjalainenInstitute for Molecular Medicine, Finland, University of Helsinki, Helsinki, Finland.
Hildigunnur KatrinardottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Run FridriksdottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Brynjar O JenssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0002-2252-4134
Vinicius TragantedeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0002-8223-8957
Egil FerkingstaddeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0001-8090-7988
Hakon JonssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0001-6197-494X
Sigurjon A GudjonssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Doruk BeyterdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Kristjan H S MooredeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0002-9579-4362
Helga B ThordardottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Snaedis KristmundsdottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0001-8981-0883
Olafur A StefanssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Solbritt Rantapää-DahlqvistDepartment of Public Health and Clinical Medicine, Rheumatology, Umea University, Umea, Sweden.ORCID 0000-0001-8259-3863
Ida Elken SonderbyDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.ORCID 0000-0001-7297-7855
Maria DidriksenDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-4856-496X
Pernilla StridhNeuroimmunology Unit, Department of Clinical Neuroscience, Center of Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-4855-0039
Jan HaavikDepartment of Biomedicine, University of Bergen, Bergen, Norway.ORCID 0000-0001-7865-2808
Laufey TryggvadottirIcelandic Cancer Registry, Icelandic Cancer Society, Reykjavik, Iceland.ORCID 0000-0001-8067-9030
Oleksandr FreiNORMENT Centre, University of Oslo, Oslo, Norway.
G Bragi WaltersdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0002-5415-6487
Ingrid KockumNeuroimmunology Unit, Department of Clinical Neuroscience, Center of Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-0867-4726
Henrik HjalgrimDepartment of Clinical Medicine, Faculty of Health, University of Copenhagen, Copenhagen, Denmark.
Thorunn A OlafsdottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0001-5454-938X
Geir SelbaekNorwegian National Centre of Ageing and Health, Vestfold Hospital Trust, Tonsberg, Norway.ORCID 0000-0001-6511-8219
Mette NyegaardDeptartment of Health Science and Technology, Aalborg University, Aalborg, Denmark.ORCID 0000-0003-4973-8543
Christian ErikstrupDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.ORCID 0000-0001-6551-6647
Thorsten BrodersenDepartment of Clinical Immunology, Zealand University Hospital, Koge, Denmark.ORCID 0000-0003-4431-9972
Saedis SaevarsdottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0001-9392-6184
Tomas OlssonNeuroimmunology Unit, Department of Clinical Neuroscience, Center of Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Kaspar Rene NielsenDepartment of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
Asgeir HaraldssonFaculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
Mie Topholm BruunDepartment of Clinical Immunology, Odense University Hospital, Odense, Denmark.ORCID 0000-0002-8819-5388
Thomas Folkmann HansenNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
DBDS Genomic Consortium
Thora SteingrimsdottirFaculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
Rikke Louise JacobsenDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-7988-7964
Rolv T LieDepartment of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.ORCID 0000-0001-6287-4051
Srdjan DjurovicDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.ORCID 0000-0002-8140-8061
Lars AlfredssonInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-1688-6697
Aitzkoa Lopez de Lapuente PortillaHematology and Transfusion Medicine, Department of Laboratory Medicine, Lund, Sweden.
Soren BrunakNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0003-0316-5866
Pall MelsteddeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Bjarni V HalldorssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0003-0756-0767
Jona SaemundsdottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Olafur Th MagnussondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Leonid PadyukovDepartment of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-2950-5670
Karina BanasikNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0003-2489-2499
Thorunn RafnardeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0003-0491-7046
Johan AsklingDepartment of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Lars KlareskogDepartment of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-9601-6186
Ole Birger PedersenDepartment of Clinical Medicine, Faculty of Health, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0003-2312-5976
Gisli MassondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Alexandra HavdahlDepartment of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.ORCID 0000-0002-9268-0423
Bjorn NilssonHematology and Transfusion Medicine, Department of Laboratory Medicine, Lund, Sweden.ORCID 0000-0001-5542-0254
Ole A AndreassenNORMENT Centre, University of Oslo, Oslo, Norway.ORCID 0000-0002-4461-3568
Mark DalyInstitute for Molecular Medicine, Finland, University of Helsinki, Helsinki, Finland.
Sisse Rye OstrowskiDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0001-5288-3851
Ingileif JonsdottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0001-8339-150X
Hreinn StefanssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Hilma HolmdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0002-9517-6636
Agnar HelgasondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Unnur ThorsteinsdottirdeCODE genetics/Amgen, Inc., Reykjavik, Iceland.
Kari StefanssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland. kstefans@decode.is.ORCID 0000-0003-1676-864X
Daniel F GudbjartssondeCODE genetics/Amgen, Inc., Reykjavik, Iceland.ORCID 0000-0002-5222-9857
deCODE Genetics (Iceland) · ISUniversity of Copenhagen · DKOslo University Hospital · NOKarolinska Institutet · SEKarolinska University Hospital · SEUniversity of Iceland · ISAalborg University Hospital · DKCopenhagen University Hospital · DKLund University · SENorwegian Institute of Public Health · NOOdense University Hospital · DKReykjavík University · ISAalborg University · DKAarhus University · DKBroad Institute · USHaukeland University Hospital · NOStatens Serum Institut · DKUmeå University · SEUniversity of Helsinki · FIZealand University Hospital Køge · DK
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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ProteinsAnimalsGenes, RecessiveGenotypeHomozygoteHumansMiceProteins
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