Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Clonal hematopoiesis in elderly twins: concordance, discordance and mortality

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Relapse risk following truncation of pegylated asparaginase in childhood acute lymphoblastic leukemia

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Cost-effectiveness targeting CLL

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Systematic dissection of transcriptional regulatory networks by genome-scale and single-cell CRISPR screens

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Structural aberrations are associated with poor survival in patients with clonal cytopenia of undetermined significance

    Research output: Contribution to journalLetterResearchpeer-review

  4. Risk of new malignancies among patients with CLL treated with chemotherapy: results of a Danish population-based study

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Clonal hematopoiesis (CH) of indeterminate potential (CHIP) is defined by mutations in myeloid cancer-associated genes with a variant allele frequency of at least 2%. Recent studies have suggested a possible genetic predisposition to CH. To further explore this phenomenon, we conducted a population-based study of 594 twins from 299 pairs aged 73-94 years, all with more than 20 years follow-up. We sequenced DNA from peripheral blood with a customized 21 genes panel at a median coverage of 6179X. The casewise concordance rates for mutations were calculated to assess genetic predisposition. Mutations were identified in 214 (36%) of the twins. Whereas 20 twin pairs had mutations within the same genes, the exact same mutation was only observed in two twin pairs. No significant difference in casewise concordance between monozygotic and dizygotic twins were found for any specific gene, subgroup or CHIP mutations overall and no significant heritability could be detected. In pairs discordant for CHIP mutations, we tested if the affected twin died before the unaffected twin, as a direct measurement of the association of having CH when controlling for familial factors. A total of 127 twin pairs were discordant for carrying a mutation, and in 61 (48%) cases the affected twin died first, p=0.72. Overall, we did not find a genetic predisposition to CHIP mutations in this twin study. The previously described negative association of CHIP mutations on survival, could not be confirmed in a direct comparison among twin pairs that were discordant for CHIP mutations.

Original languageEnglish
JournalBlood
Volume135
Issue number4
Pages (from-to)261-268
Number of pages8
ISSN0006-4971
DOIs
Publication statusPublished - 2020

Bibliographical note

© 2020 by The American Society of Hematology.

    Research areas

  • Aged, Aged, 80 and over, Cohort Studies, Diseases in Twins/genetics, Female, Gene Frequency, Genetic Predisposition to Disease, Hematologic Neoplasms/genetics, Hematopoiesis, Humans, Leukemia, Myeloid/genetics, Male, Mutation, Twins, Dizygotic/genetics, Twins, Monozygotic/genetics, Twins/genetics

ID: 58982417