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Clonal hematopoiesis in elderly twins: concordance, discordance and mortality

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Hansen, Jakob Werner ; Pedersen, Dorthe Almind ; Larsen, Lisbeth Aagaard ; Husby, Simon ; Clemmensen, Signe Bedsted ; Hjelmborg, Jacob ; Favero, Francesco ; Weischenfeldt, Joachim ; Christensen, Kaare ; Grønbæk, Kirsten. / Clonal hematopoiesis in elderly twins : concordance, discordance and mortality. In: Blood. 2020 ; Vol. 135, No. 4. pp. 261-268.

Bibtex

@article{f9fb212c0dbe4edcaef7bf1f1fdd9b03,
title = "Clonal hematopoiesis in elderly twins: concordance, discordance and mortality",
abstract = "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.",
keywords = "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",
author = "Hansen, {Jakob Werner} and Pedersen, {Dorthe Almind} and Larsen, {Lisbeth Aagaard} and Simon Husby and Clemmensen, {Signe Bedsted} and Jacob Hjelmborg and Francesco Favero and Joachim Weischenfeldt and Kaare Christensen and Kirsten Gr{\o}nb{\ae}k",
note = "{\textcopyright} 2020 by The American Society of Hematology.",
year = "2020",
doi = "10.1182/blood.2019001793",
language = "English",
volume = "135",
pages = "261--268",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "4",

}

RIS

TY - JOUR

T1 - Clonal hematopoiesis in elderly twins

T2 - concordance, discordance and mortality

AU - Hansen, Jakob Werner

AU - Pedersen, Dorthe Almind

AU - Larsen, Lisbeth Aagaard

AU - Husby, Simon

AU - Clemmensen, Signe Bedsted

AU - Hjelmborg, Jacob

AU - Favero, Francesco

AU - Weischenfeldt, Joachim

AU - Christensen, Kaare

AU - Grønbæk, Kirsten

N1 - © 2020 by The American Society of Hematology.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Cohort Studies

KW - Diseases in Twins/genetics

KW - Female

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - Hematologic Neoplasms/genetics

KW - Hematopoiesis

KW - Humans

KW - Leukemia, Myeloid/genetics

KW - Male

KW - Mutation

KW - Twins, Dizygotic/genetics

KW - Twins, Monozygotic/genetics

KW - Twins/genetics

UR - http://www.scopus.com/inward/record.url?scp=85078392581&partnerID=8YFLogxK

U2 - 10.1182/blood.2019001793

DO - 10.1182/blood.2019001793

M3 - Journal article

C2 - 31697811

VL - 135

SP - 261

EP - 268

JO - Blood

JF - Blood

SN - 0006-4971

IS - 4

ER -

ID: 58982417