MR-link-2: pleiotropy robust cis Mendelian randomization validated in three independent reference datasets of causality
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| Publicat a: | Nature Communications vol. 16, no. 1 (2025), p. 6112 |
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| Altres autors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| 022 | |a 2041-1723 | ||
| 024 | 7 | |a 10.1038/s41467-025-60868-1 |2 doi | |
| 035 | |a 3226850372 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
| 084 | |a 145839 |2 nlm | ||
| 100 | 1 | |a van der Graaf, Adriaan |u University of Lausanne, Department of Computational Biology, Lausanne, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204); Swiss Institute of Bioinformatics, Lausanne, Switzerland (GRID:grid.419765.8) (ISNI:0000 0001 2223 3006) | |
| 245 | 1 | |a MR-link-2: pleiotropy robust <i>cis</i> Mendelian randomization validated in three independent reference datasets of causality | |
| 260 | |b Nature Publishing Group |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Mendelian randomization (MR) identifies causal relationships from observational data but has increased Type 1 error rates (T1E) when genetic instruments are limited to a single associated region, a typical scenario for molecular exposures. We developed MR-link-2, which leverages summary statistics and linkage disequilibrium (LD) to estimate causal effects and pleiotropy in a single region. We compare MR-link-2 to other cis MR methods: i) In simulations, MR-link-2 has calibrated T1E and high power. ii) We reidentify metabolic reactions from three metabolic pathway references using four independent metabolite quantitative trait locus studies. MR-link-2 often (76%) outperforms other methods in area under the receiver operator characteristic curve (AUC) (up to 0.80). iii) For canonical causal relationships between complex traits, MR-link-2 has lower per-locus T1E (0.096 vs. min. 0.142, at 5% level), identifying all but one of the true causal links, reducing cross-locus causal effect heterogeneity to almost half. iv) Testing causal direction between blood cell compositions and marker gene expression shows MR-link-2 has superior AUC (0.82 vs. 0.68). Finally, analyzing causality between metabolites not directly connected by canonical reactions, only MR-link-2 identifies the causal relationship between pyruvate and citrate (α̂<inline-graphic specific-use="web" mime-subtype="GIF" xlink:href="41467_2025_60868_Article_IEq1.gif" /> = 0.11, P =  7.2⋅10−7), a key citric acid cycle reaction. Overall, MR-link-2 identifies pleiotropy-robust causality from summary statistics in single associated regions, making it well suited for applications to molecular phenotypes.Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical scenario when assessing molecular traits like protein or metabolite levels as risk factors. Here the authors introduce a single-region pleiotropy-robust MR method, validating the method on three ground truth sources, showing its capability to identify disease-causing molecular traits. | |
| 653 | |a Statistics | ||
| 653 | |a Pleiotropy | ||
| 653 | |a Pyruvic acid | ||
| 653 | |a Violations | ||
| 653 | |a Datasets | ||
| 653 | |a Quantitative trait loci | ||
| 653 | |a Genetic variance | ||
| 653 | |a Phenotypes | ||
| 653 | |a Causality | ||
| 653 | |a Metabolites | ||
| 653 | |a Linkage disequilibrium | ||
| 653 | |a Gene mapping | ||
| 653 | |a Genes | ||
| 653 | |a Blood | ||
| 653 | |a Citric acid | ||
| 653 | |a Heterogeneity | ||
| 653 | |a Simulation | ||
| 653 | |a Metabolic pathways | ||
| 653 | |a Gene expression | ||
| 653 | |a Risk factors | ||
| 653 | |a Randomization | ||
| 653 | |a Methods | ||
| 653 | |a Robustness (mathematics) | ||
| 653 | |a Tricarboxylic acid cycle | ||
| 653 | |a Blood cells | ||
| 653 | |a Meta-analysis | ||
| 653 | |a Genetic diversity | ||
| 653 | |a Social | ||
| 700 | 1 | |a Warmerdam, Robert |u University of Groningen, Department of Genetics, Groningen, The Netherlands (GRID:grid.4830.f) (ISNI:0000 0004 0407 1981); Oncode institute, Utrecht, The Netherlands (GRID:grid.499559.d) | |
| 700 | 1 | |a Auwerx, Chiara |u University of Lausanne, Department of Computational Biology, Lausanne, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204); Swiss Institute of Bioinformatics, Lausanne, Switzerland (GRID:grid.419765.8) (ISNI:0000 0001 2223 3006); University of Lausanne, Center for Integrative Genomics, Lausanne, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204) | |
| 700 | 1 | |a Boltz, Toni |u University of California Los Angeles, Department of Human Genetics, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0001 2167 8097) | |
| 700 | 1 | |a Boomsma, Dorret I. |u Amsterdam Reproduction & Development (AR&D) research institute, Amsterdam, the Netherlands (GRID:grid.19006.3e); Amsterdam Public Health research institute, Amsterdam, the Netherlands (GRID:grid.16872.3a) (ISNI:0000 0004 0435 165X); Vrije Universiteit Amsterdam, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) | |
| 700 | 1 | |a Brown, Andrew |u University of Dundee, Population Health and Genomics, Dundee, UK (GRID:grid.8241.f) (ISNI:0000 0004 0397 2876) | |
| 700 | 1 | |a Cheruiyot, Evans |u The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) | |
| 700 | 1 | |a Davenport, Emma E. |u Wellcome Genome Campus, Wellcome Sanger Institute, Hinxton, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382) | |
| 700 | 1 | |a Dupuis, Théo |u University of Dundee, Population Health and Genomics, Dundee, UK (GRID:grid.8241.f) (ISNI:0000 0004 0397 2876) | |
| 700 | 1 | |a Esko, Tõnu |u University of Tartu, Estonian Genome Centre, Institute of Genomics, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661) | |
| 700 | 1 | |a Farzeen, Aiman |u Helmholtz Munich, Institute of Neurogenomics, Computational Health Center, Neuherberg, Germany (GRID:grid.10939.32); Helmholtz Zentrum München - German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525); Helmholtz Zentrum München - German Research Center for Environmental Health, Institute of Epidemiology, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525) | |
| 700 | 1 | |a Ferrucci, Luigi |u National Institutes of Health, Translational Gerontology Branch, National Institute on Aging, Baltimore, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) | |
| 700 | 1 | |a Frayling, Timothy M. |u University of Geneva, Department of Genetic Medicine and Development, CMU, Geneva, Switzerland (GRID:grid.8591.5) (ISNI:0000 0001 2175 2154) | |
| 700 | 1 | |a Gibson, Greg |u Georgia Institute of Technology, Center for Integrative Genomics, Atlanta, USA (GRID:grid.213917.f) (ISNI:0000 0001 2097 4943) | |
| 700 | 1 | |a Gieger, Christian |u Helmholtz Zentrum München - German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525); Helmholtz Zentrum München - German Research Center for Environmental Health, Institute of Epidemiology, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525) | |
| 700 | 1 | |a van Greevenbroek, Marleen |u Maastricht University, CARIM, Maastricht, The Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099) | |
| 700 | 1 | |a Mishra, Binisha Hamal |u Tampere University, Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0005 0718 6722); Tampere University, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0005 0718 6722); Fimlab Laboratories, Department of Clinical Chemistry, Tampere, Finland (GRID:grid.511163.1) (ISNI:0000 0004 0518 4910) | |
| 700 | 1 | |a Ikram, M. Arfan |u Erasmus MC University Medical Center, Department of Epidemiology, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X) | |
| 700 | 1 | |a Inouye, Michael |u University of Cambridge, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); University of Cambridge, Victor Phillip Dahdaleh Heart and Lung Research Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); University of Cambridge, Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); Baker Heart and Diabetes Institute, Cambridge Baker Systems Genomics Initiative, Melbourne, Australia (GRID:grid.1051.5) (ISNI:0000 0000 9760 5620); Wellcome Genome Campus and University of Cambridge, Health Data Research UK Cambridge, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); University of Cambridge, British Heart Foundation Centre of Research Excellence, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934) | |
| 700 | 1 | |a Jansen, Rick |u Amsterdam Public Health research institute, Amsterdam, the Netherlands (GRID:grid.16872.3a) (ISNI:0000 0004 0435 165X); Stress & Sleep, Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry & Amsterdam Neuroscience -Complex Trait Genetics (VUmc) and Mood, Anxiety, Psychosis, Amsterdam, The Netherlands (GRID:grid.16872.3a) (ISNI:0000 0004 0435 165X) | |
| 700 | 1 | |a Kähönen, Mika |u Tampere University, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0005 0718 6722); Tampere University Hospital, Department of Clinical Physiology, Tampere, Finland (GRID:grid.412330.7) (ISNI:0000 0004 0628 2985) | |
| 700 | 1 | |a Kukushkina, Viktorija |u University of Tartu, Estonian Genome Centre, Institute of Genomics, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661) | |
| 700 | 1 | |a Lapinska, Sandra |u University of California Los Angeles, Bioinformatics Interdepartmental Program, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0001 2167 8097) | |
| 700 | 1 | |a Lehtimäki, Terho |u Tampere University, Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0005 0718 6722); Tampere University, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0005 0718 6722); Fimlab Laboratories, Department of Clinical Chemistry, Tampere, Finland (GRID:grid.511163.1) (ISNI:0000 0004 0518 4910) | |
| 700 | 1 | |a Mägi, Reedik |u University of Tartu, Estonian Genome Centre, Institute of Genomics, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661) | |
| 700 | 1 | |a Martinez-Perez, Angel |u Institut de Recerca Sant Pau (IR Sant Pau), Unit of Genomic of Complex Diseases, Barcelona, Spain (GRID:grid.530448.e) (ISNI:0000 0005 0709 4625) | |
| 700 | 1 | |a McRae, Allan F. |u The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) | |
| 700 | 1 | |a van Meurs, Joyce |u Erasmus MC University Medical Center, Department of Internal Medicine, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X); Erasmus MC University Medical Center, Department of Orthopaedics and Sportsmedicine, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X) | |
| 700 | 1 | |a Milani, Lili |u University of Tartu, Estonian Genome Centre, Institute of Genomics, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661) | |
| 700 | 1 | |a Montgomery, Grant W. |u The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) | |
| 700 | 1 | |a Nagpal, Sini |u Georgia Institute of Technology, Center for Integrative Genomics, Atlanta, USA (GRID:grid.213917.f) (ISNI:0000 0001 2097 4943) | |
| 700 | 1 | |a Nauck, Matthias |u University Medicine Greifswald, Institute of Clinical Chemistry and Laboratory Medicine, Greifswald, Germany (GRID:grid.412469.c) (ISNI:0000 0000 9116 8976) | |
| 700 | 1 | |a Ophoff, Roel |u University of California Los Angeles, Department of Human Genetics, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0001 2167 8097); University of California Los Angeles, Bioinformatics Interdepartmental Program, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0001 2167 8097); University of California Los Angeles, Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0001 2167 8097) | |
| 700 | 1 | |a Pasaniuc, Bogdan |u University of California Los Angeles, Department of Human Genetics, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0001 2167 8097); University of California Los Angeles, Bioinformatics Interdepartmental Program, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0001 2167 8097); University of California Los Angeles, Department of Computational Medicine, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0001 2167 8097); University of California Los Angeles, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0001 2167 8097) | |
| 700 | 1 | |a Paul, Dirk S. |u University of Cambridge, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); University of Cambridge, Victor Phillip Dahdaleh Heart and Lung Research Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); AstraZeneca, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, Cambridge, UK (GRID:grid.417815.e) (ISNI:0000 0004 5929 4381) | |
| 700 | 1 | |a Persyn, Elodie |u University of Cambridge, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); University of Cambridge, Victor Phillip Dahdaleh Heart and Lung Research Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); University of Cambridge, Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934) | |
| 700 | 1 | |a Peters, Annette |u Helmholtz Zentrum München - German Research Center for Environmental Health, Institute of Epidemiology, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525); LMU Munich, Chair of Epidemiology, IBE, Faculty of Medicine, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X); Partner Site Munich Heart Alliance, German Centre for Cardiovascular Research (DZHK), Munich, Germany (GRID:grid.452396.f) (ISNI:0000 0004 5937 5237); German Center for Diabetes Research (DZD), Neuherberg, Germany (GRID:grid.452622.5) | |
| 700 | 1 | |a Prokisch, Holger |u Helmholtz Munich, Institute of Neurogenomics, Computational Health Center, Neuherberg, Germany (GRID:grid.452622.5); Technical University of Munich, School of Medicine, Institute of Human Genetics, Munich, Germany (GRID:grid.6936.a) (ISNI:0000 0001 2322 2966); partner site Munich, German Center for Child and Adolescent Health (DZKJ), Munich, Germany (GRID:grid.6936.a) | |
| 700 | 1 | |a Raitakari, Olli T. |u University of Turku, Research centre of Applied and Preventive Cardiovascular Medicine, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371); Turku University Hospital, Department of Clinical Physiology and Nuclear Medicine, Turku, Finland (GRID:grid.410552.7) (ISNI:0000 0004 0628 215X); University of Turku and Turku University Hospital, Centre for Population Health Research, Turku, Finland (GRID:grid.410552.7) (ISNI:0000 0004 0628 215X); University of Turku, InFLAMES Research Flagship, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371) | |
| 700 | 1 | |a Raitoharju, Emma |u Tampere University, Molecular Epidemiology, Faculty of Medicine and Health Technology, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0005 0718 6722); Tampere University Hospital, Tampere, Finland (GRID:grid.412330.7) (ISNI:0000 0004 0628 2985) | |
| 700 | 1 | |a Singleton, Andrew |u National Institutes of Health, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) | |
| 700 | 1 | |a Slagboom, Eline |u Leiden University Medical Center, Section of Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden, the Netherlands (GRID:grid.10419.3d) (ISNI:0000 0000 8945 2978) | |
| 700 | 1 | |a Soria, José Manuel |u Institut de Recerca Sant Pau (IR Sant Pau), Unit of Genomic of Complex Diseases, Barcelona, Spain (GRID:grid.530448.e) (ISNI:0000 0005 0709 4625) | |
| 700 | 1 | |a Souto, Juan Carlos |u Institut de Recerca Sant Pau (IR Sant Pau), Unit of Genomic of Complex Diseases, Barcelona, Spain (GRID:grid.530448.e) (ISNI:0000 0005 0709 4625) | |
| 700 | 1 | |a Teumer, Alexander |u University Medicine Greifswald, Department of Psychiatry and Psychotherapy, Greifswald, Germany (GRID:grid.412469.c) (ISNI:0000 0000 9116 8976); Partner Site Greifswald, DZHK (German Center for Cardiovascular Research), Greifswald, Germany (GRID:grid.452396.f) (ISNI:0000 0004 5937 5237); Medical University of Bialystok, Department of Population Medicine and Lifestyle Diseases Prevention, Bialystok, Poland (GRID:grid.48324.39) (ISNI:0000 0001 2248 2838) | |
| 700 | 1 | |a Tokolyi, Alex |u Wellcome Genome Campus, Wellcome Sanger Institute, Hinxton, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382) | |
| 700 | 1 | |a Veldink, Jan |u UMC Utrecht Brain Center Rudolf Magnus, Department of Neurology, Utrecht, The Netherlands (GRID:grid.7692.a) (ISNI:0000 0000 9012 6352) | |
| 700 | 1 | |a Verlouw, Joost |u Erasmus MC University Medical Center, Department of Internal Medicine, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X) | |
| 700 | 1 | |a Viñuela, Ana |u University of Newcastle, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK (GRID:grid.1006.7) (ISNI:0000 0001 0462 7212) | |
| 700 | 1 | |a Visscher, Peter M. |u The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) | |
| 700 | 1 | |a Völker, Uwe |u Partner Site Greifswald, DZHK (German Center for Cardiovascular Research), Greifswald, Germany (GRID:grid.452396.f) (ISNI:0000 0004 5937 5237); University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany (GRID:grid.412469.c) (ISNI:0000 0000 9116 8976) | |
| 700 | 1 | |a Weiss, Stefan |u University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany (GRID:grid.412469.c) (ISNI:0000 0000 9116 8976) | |
| 700 | 1 | |a Westra, Harm-Jan |u University of Groningen, Department of Genetics, Groningen, The Netherlands (GRID:grid.4830.f) (ISNI:0000 0004 0407 1981); Oncode institute, Utrecht, The Netherlands (GRID:grid.499559.d) | |
| 700 | 1 | |a Wood, Andrew R. |u University of Exeter, College of Medicine and Health, Exeter, UK (GRID:grid.8391.3) (ISNI:0000 0004 1936 8024) | |
| 700 | 1 | |a Xie, Manke |u Georgia Institute of Technology, Center for Integrative Genomics, Atlanta, USA (GRID:grid.213917.f) (ISNI:0000 0001 2097 4943) | |
| 700 | 1 | |a Võsa, Urmo |u University of Tartu, Estonian Genome Centre, Institute of Genomics, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661) | |
| 700 | 1 | |a Borges, Maria Carolina |u University of Bristol, MRC Integrative Epidemiology Unit, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) | |
| 700 | 1 | |a Franke, Lude |u University of Groningen, Department of Genetics, Groningen, The Netherlands (GRID:grid.4830.f) (ISNI:0000 0004 0407 1981); Oncode institute, Utrecht, The Netherlands (GRID:grid.499559.d) | |
| 700 | 1 | |a Kutalik, Zoltán |u University of Lausanne, Department of Computational Biology, Lausanne, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204); Swiss Institute of Bioinformatics, Lausanne, Switzerland (GRID:grid.419765.8) (ISNI:0000 0001 2223 3006); University Center for Primary Care and Public Health, Lausanne, Switzerland (GRID:grid.511931.e) (ISNI:0000 0004 8513 0292) | |
| 773 | 0 | |t Nature Communications |g vol. 16, no. 1 (2025), p. 6112 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
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