GREGoR: accelerating genomics for rare diseases

Moez Dawood, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA. mdawood@bcm.edu.
Ben Heavner, Department of Biostatistics, University of Washington, Seattle, WA, USA.
Marsha M. Wheeler, Department of Biostatistics, University of Washington, Seattle, WA, USA.
Rachel A. Ungar, Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA.
Jonathan LoTempio, Institute for Clinical and Translational Science, University of California, Irvine, Irvine, CA, USA.
Laurens Wiel, Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA.
Seth Berger, Division of Genetics and Metabolism, Children's National Hospital, Washington, DC, USA.
Jonathan A. Bernstein, Department of Pediatrics, Division of Medical Genetics, Stanford University, Stanford, CA, USA.
Jessica X. Chong, Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA, USA.
Emmanuèle C. Délot, Institute for Clinical and Translational Science, University of California, Irvine, Irvine, CA, USA.
Evan E. Eichler, Department of Genome Sciences, University of Washington, Seattle, WA, USA.
James R. Lupski, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Ali Shojaie, Department of Biostatistics, University of Washington, Seattle, WA, USA.
Michael E. Talkowski, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Alex H. Wagner, Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Chia-Lin Wei, Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Christopher Wellington, Office of Genomic Data Science, National Human Genome Research Institute, Bethesda, MD, USA.
Matthew T. Wheeler, Division of Cardiovascular Medicine, School of Medicine, Stanford University, Stanford, CA, USA.

Document Type

Journal Article

Publication Date

11-1-2025

Journal

Nature

Volume

647

Issue

8089

DOI

10.1038/s41586-025-09613-8

Abstract

Rare diseases are collectively common, affecting approximately 1 in 20 individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in next-generation sequencing, development of new computational and functional genomics approaches to prioritize genes and variants and increased global sharing of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis. The Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium was initiated to study thousands of challenging rare disease cases and families and apply, standardize and evaluate emerging genomics technologies and analytics to accelerate their adoption in clinical practice. Furthermore, all data generated, currently representing over 7,500 individuals from over 3,000 families, are rapidly made available to researchers worldwide through the Analysis, Visualization and Informatics Lab-space (AnVIL) to catalyse global efforts to develop approaches for genetic diagnoses in rare diseases. Most of these families have undergone previous clinical genetic testing but remained unsolved, with most being exome-negative. Here we describe the collaborative research framework, datasets and discoveries comprising GREGoR that will provide foundational resources and substrates for the future of rare disease genomics.

Department

Pediatrics

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