Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits.

Address: Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine, University of Freiburg, Freiburg, Germany.; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Centre for Integrative Biological Signalling Studies, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Department of Medicine IV, Nephrology and Primary Care, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine, University of Freiburg, Freiburg, Germany.; Department of Medicine IV, Nephrology and Primary Care, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Research, Maze Therapeutics, South San Francisco, CA, USA.; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Department of Medicine IV, Nephrology and Primary Care, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; SYNLAB MVZ Humangenetik Freiburg, Freiburg, Germany.; Centre for Integrative Biological Signalling Studies, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.; Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Centre for Integrative Biological Signalling Studies, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.; Department of Medicine IV, Nephrology and Primary Care, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.; Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; School of Medicine, University of Galway, Galway, Ireland.; Ryan Institute, University of Galway, Galway, Ireland.; Division of Microbiology, University of Galway, Galway, Ireland.; APC Microbiome Ireland, Cork, Ireland.; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. [email protected].; German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany. [email protected].; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany. [email protected].; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. [email protected].; Centre for Integrative Biological Signalling Studies, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany. [email protected].