Optimized summary-statistic-based single-cell eQTL meta-analysis
Scientific Reports, vol. 15, pp. 28407
Abstract
The identification of expression quantitative trait loci (eQTLs) holds great potential to improve the interpretation of disease-associated genetic variation. As many such disease-associated variants act in a context-, tissue- or even cell-type-specific manner, single-cell RNA-sequencing (scRNA-seq) data is uniquely suitable for identifying the specific cell type or context in which these genetic variants act. However, due to the limited sample sizes in single-cell studies, discovery of cell-type-specific eQTLs is now limited. To improve power to detect such eQTLs, large-scale joint analyses are needed. These are however, complicated by privacy constraints due to sharing of genotype data and the measurement and technical variety across different scRNA-seq datasets as a result of differences in mRNA capture efficiency, experimental protocols, and sequencing strategies. A solution to these issues is a federated weighted meta-analysis (WMA) approach in which summary statistics are integrated using dataset-specific weights. Here, we compare different strategies and provide best practice recommendations for eQTL WMA across scRNA-seq datasets.
Authors 37
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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University Medical Center Groningen · University of Groningen · Oncode Institute
Affiliation as printed
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Oncode Institute, Utrecht, The Netherlands
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University Medical Center Groningen · University of Groningen · Oncode Institute
Affiliation as printed
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Oncode Institute, Utrecht, The Netherlands
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University Medical Center Groningen · University of Groningen · Oncode Institute
Affiliation as printed
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Oncode Institute, Utrecht, The Netherlands
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University Medical Center Groningen · University of Groningen · Oncode Institute
Affiliation as printed
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Oncode Institute, Utrecht, The Netherlands
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University Medical Center Groningen · University of Groningen · German Cancer Research Center · Oncode Institute · European Molecular Biology Laboratory
Affiliation as printed
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. m.j.bonder@umcg.nl
Division of Computational Genomics and Systems Genetics, German Cancer Research Center, Heidelberg, Germany. m.j.bonder@umcg.nl
Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. m.j.bonder@umcg.nl
Oncode Institute, Utrecht, The Netherlands. m.j.bonder@umcg.nl
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Division of Computational Genomics and Systems Genetics, German Cancer Research Center, Heidelberg, Germany
Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
Oncode Institute, Utrecht, The Netherlands
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Garvan Institute of Medical Research · The University of Queensland · Institute for Molecular Bioscience
Affiliation as printed
Computational Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Genetics , University of Groningen , University Medical Center Groningen , Groningen , The Netherlands
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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University Medical Center Groningen · University of Groningen · Oncode Institute
Affiliation as printed
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Oncode Institute, Utrecht, The Netherlands
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Affiliation as printed
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
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Leiden University Medical Center · Delft University of Technology
Affiliation as printed
Delft Bioinformatics Laboratory, Delft University of Technology, Delft, The Netherlands
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
Leiden Computational Biology Center, Leiden University Medical Center, Leiden, The Netherlands
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Garvan Institute of Medical Research
Affiliation as printed
Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia
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University Medical Center Groningen · University of Groningen · Oncode Institute
Affiliation as printed
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Oncode Institute, Utrecht, The Netherlands
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Barcelona Supercomputing Center
Affiliation as printed
Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Catalonia, Spain
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University Medical Center Groningen · University of Groningen · Oncode Institute
Affiliation as printed
Department of Genetics , University of Groningen , University Medical Center Groningen , Groningen , The Netherlands
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Oncode Institute, Utrecht, The Netherlands
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RIKEN Center for Integrative Medical Sciences
Affiliation as printed
Laboratory for Genome Information Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Affiliation as printed
Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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University Medical Center Utrecht
Affiliation as printed
Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
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RIKEN Center for Integrative Medical Sciences
Affiliation as printed
Laboratory for Genome Information Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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Affiliation as printed
Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
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Affiliation as printed
Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
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RIKEN Center for Integrative Medical Sciences
Affiliation as printed
Laboratory for Genome Information Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
GRIAC Research Institute, University Medical Center Groningen, Groningen, the Netherlands
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German Cancer Research Center · Wellcome Sanger Institute · European Molecular Biology Laboratory
Affiliation as printed
Division of Computational Genomics and Systems Genetics , German Cancer Research Center , Heidelberg , Germany
Genome Biology Unit , European Molecular Biology Laboratory , Heidelberg , Germany
Division of Computational Genomics and Systems Genetics, German Cancer Research Center, Heidelberg, Germany
Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
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Affiliation as printed
Samsung Genome Institute, Samsung Medical Center, Seoul, Korea
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Agency for Science, Technology and Research · Genome Institute of Singapore
Affiliation as printed
A*STAR Genome Institute of Singapore, Singapore, Singapore
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Affiliation as printed
Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
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Agency for Science, Technology and Research · Genome Institute of Singapore
Affiliation as printed
A*STAR Genome Institute of Singapore, Singapore, Singapore
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Affiliation as printed
Open Targets, Wellcome Genome Campus, Cambridge, UK
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Garvan Institute of Medical Research
Affiliation as printed
Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia
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University of California, San Francisco · University of California San Francisco Medical Center
Affiliation as printed
Institute for Human Genetics, University of California San Francisco, San Francisco, USA
UCSF Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
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Brigham and Women's Hospital · Harvard University
Affiliation as printed
Evergrande Center for Immunologic Disease, Harvard Medical School and Brigham and Women's Hospital, Boston, USA
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Leiden University Medical Center · Delft University of Technology
Affiliation as printed
Delft Bioinformatics Laboratory, Delft University of Technology, Delft, The Netherlands
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
Leiden Computational Biology Center, Leiden University Medical Center, Leiden, The Netherlands
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Barcelona Supercomputing Center
Affiliation as printed
Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Catalonia, Spain
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Affiliation as printed
UNSW Cellular Genomics Futures Institute, University of New South Wales, Sydney, Australia
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