UK Biobank WES of whole blood–derived DNA was performed using Illumina NovaSeq 6000 platform at the Regeneron Sequencing Center (Tarrytown, NY) as described previously (30 (link)). TOPMed WGS to an average depth of 38× was performed using whole blood–derived DNA, PCR-free library construction, and Illumina HiSeq X technology as described elsewhere (29 (link)). CHIP mutations were called previously in TOPMed (28 (link)) and UK Biobank (26 (link)). CHIP mutations were reevaluated after the error-corrected release of WES in UK Biobank in June 2020. Briefly, CHIP mutations were detected with GATK MuTect2 software (49 (link)) with parameters as previously described (28 (link)). Samples were annotated as having CHIP if Mutect2 identifies one or more of a prespecified list of pathogenic somatic variants (23 (link), 24 (link)). Common germline variants and sequencing artifacts were excluded as before. Each study includes both the presence of (i) any CHIP and (ii) CHIP with VAF > 0.1, as larger CHIP clones above this threshold have previously been more strongly associated with adverse clinical outcomes (24 (link), 26 (link)).
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Other organizations :
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Vanderbilt University, Johns Hopkins University, Yale University, Lund University, Washington State University, University of Minnesota Medical Center, University of Michigan–Ann Arbor, Stanford University, VA Palo Alto Health Care System, University of Washington, National Institute for Health Research, University of Leicester, Glenfield Hospital, Vanderbilt University Medical Center, The University of Texas Rio Grande Valley, Wake Forest University, University of Alabama at Birmingham, University of Colorado Anschutz Medical Campus, University of Colorado Denver, Johns Hopkins Medicine, The University of Texas Health Science Center at Houston, Washington University in St. Louis, Boston University, National University of Samoa, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, University of North Carolina at Chapel Hill, Vitalant, UCSF Benioff Children's Hospital, Pacific Research Institute, University of Mississippi Medical Center, Jackson Memorial Hospital, Northwestern University, Bloodworks Northwest, Icahn School of Medicine at Mount Sinai, University of Vermont, Cornell University, VA Office of Research and Development, Kaiser Permanente Washington Health Research Institute, Tulane University, National Heart Lung and Blood Institute, Framingham Heart Study, University of Pittsburgh, University of Cincinnati Medical Center, University of Cincinnati, American Samoa Government, Baylor College of Medicine, Genomic Health (United States), University of Virginia, Augusta University, University of Maryland, Baltimore, Circadian (United States), Beth Israel Deaconess Medical Center, Regeneron (United States), University of Kentucky, University of Illinois Chicago, Brown University, Providence College, Mayo Clinic in Florida, UCLA Medical Center, Harbor–UCLA Medical Center, Albert Einstein College of Medicine, Fred Hutch Cancer Center, University of Arizona, Brown Foundation, Novo Nordisk Foundation, University of Copenhagen, Health Data Research UK, University of Cambridge, British Heart Foundation, Howard Hughes Medical Institute
Positive control: Prespecified list of pathogenic somatic variants for CHIP detection
Negative control: Exclusion of common germline variants and sequencing artifacts
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