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Birth Weight Is Associated With Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Outcomes in Adulthood

Schuermans, Art ; Nakao, Tetsushi ; Ruan, Yunfeng ; Koyama, Satoshi LU orcid ; Yu, Zhi ; Uddin, Md Mesbah ; Haidermota, Sara ; Hornsby, Whitney ; Lewandowski, Adam J. and Bick, Alexander G. , et al. (2023) In Journal of the American Heart Association 12(13).
Abstract

BACKGROUND: High and low birth weight are independently associated with increased cardiovascular disease risk in adulthood. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic cells with preleu-kemic somatic mutations, predicts incident cardiovascular disease independent of traditional cardiovascular risk factors. Whether birth weight predicts development of CHIP later in life is unknown. METHODS AND RESULTS: A total of 221 047 adults enrolled in the UK Biobank with whole exome sequences and self-reported birth weight were analyzed. Of those, 22 030 (11.5%) had low (<2.5 kg) and 29 292 (14.7%) high birth weight (>4.0 kg). CHIP prevalence was higher among participants with low... (More)

BACKGROUND: High and low birth weight are independently associated with increased cardiovascular disease risk in adulthood. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic cells with preleu-kemic somatic mutations, predicts incident cardiovascular disease independent of traditional cardiovascular risk factors. Whether birth weight predicts development of CHIP later in life is unknown. METHODS AND RESULTS: A total of 221 047 adults enrolled in the UK Biobank with whole exome sequences and self-reported birth weight were analyzed. Of those, 22 030 (11.5%) had low (<2.5 kg) and 29 292 (14.7%) high birth weight (>4.0 kg). CHIP prevalence was higher among participants with low (6.0%, P=0.049) and high (6.3%, P<0.001) versus normal birth weight (5.7%, ref.). Multivariable-adjusted logistic regression analyses demonstrated that each 1-kg increase in birth weight was associated with a 3% increased risk of CHIP (odds ratio, 1.03 [95% CI, 1.00–1.06]; P=0.04), driven by a stronger association ob-served between birth weight and DNMT3A CHIP (odds ratio, 1.04 per 1-kg increase [95% CI, 1.01–1.08]; P=0.02). Mendelian randomization analyses supported a causal relationship of longer gestational age at delivery with DNMT3A CHIP. Multivariable Cox regression demonstrated that CHIP was independently and additively associated with incident cardiovascular disease or death across birth weight groups, with highest absolute risks in those with CHIP plus high or low birth weight. CONCLUSIONS: Higher birth weight is associated with increased risk of developing CHIP in midlife, especially DNMT3A CHIP. These findings identify a novel risk factor for CHIP and provide insights into the relationships among early-life environment, CHIP, cancer, and cardiovascular disease.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
birth weight, cardiovascular disease, clonal hematopoiesis, early life, genetics
in
Journal of the American Heart Association
volume
12
issue
13
article number
e030220
publisher
Wiley-Blackwell
external identifiers
  • pmid:37345823
  • scopus:85164235782
ISSN
2047-9980
DOI
10.1161/JAHA.123.030220
language
English
LU publication?
yes
id
ce0c9de5-4f8c-4c8b-b3a1-48ff1099c060
date added to LUP
2023-09-06 14:27:56
date last changed
2024-10-05 20:00:09
@article{ce0c9de5-4f8c-4c8b-b3a1-48ff1099c060,
  abstract     = {{<p>BACKGROUND: High and low birth weight are independently associated with increased cardiovascular disease risk in adulthood. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic cells with preleu-kemic somatic mutations, predicts incident cardiovascular disease independent of traditional cardiovascular risk factors. Whether birth weight predicts development of CHIP later in life is unknown. METHODS AND RESULTS: A total of 221 047 adults enrolled in the UK Biobank with whole exome sequences and self-reported birth weight were analyzed. Of those, 22 030 (11.5%) had low (&lt;2.5 kg) and 29 292 (14.7%) high birth weight (&gt;4.0 kg). CHIP prevalence was higher among participants with low (6.0%, P=0.049) and high (6.3%, P&lt;0.001) versus normal birth weight (5.7%, ref.). Multivariable-adjusted logistic regression analyses demonstrated that each 1-kg increase in birth weight was associated with a 3% increased risk of CHIP (odds ratio, 1.03 [95% CI, 1.00–1.06]; P=0.04), driven by a stronger association ob-served between birth weight and DNMT3A CHIP (odds ratio, 1.04 per 1-kg increase [95% CI, 1.01–1.08]; P=0.02). Mendelian randomization analyses supported a causal relationship of longer gestational age at delivery with DNMT3A CHIP. Multivariable Cox regression demonstrated that CHIP was independently and additively associated with incident cardiovascular disease or death across birth weight groups, with highest absolute risks in those with CHIP plus high or low birth weight. CONCLUSIONS: Higher birth weight is associated with increased risk of developing CHIP in midlife, especially DNMT3A CHIP. These findings identify a novel risk factor for CHIP and provide insights into the relationships among early-life environment, CHIP, cancer, and cardiovascular disease.</p>}},
  author       = {{Schuermans, Art and Nakao, Tetsushi and Ruan, Yunfeng and Koyama, Satoshi and Yu, Zhi and Uddin, Md Mesbah and Haidermota, Sara and Hornsby, Whitney and Lewandowski, Adam J. and Bick, Alexander G. and Niroula, Abhishek and Jaiswal, Siddhartha and Ebert, Benjamin L. and Natarajan, Pradeep and Honigberg, Michael C.}},
  issn         = {{2047-9980}},
  keywords     = {{birth weight; cardiovascular disease; clonal hematopoiesis; early life; genetics}},
  language     = {{eng}},
  number       = {{13}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{Birth Weight Is Associated With Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Outcomes in Adulthood}},
  url          = {{http://dx.doi.org/10.1161/JAHA.123.030220}},
  doi          = {{10.1161/JAHA.123.030220}},
  volume       = {{12}},
  year         = {{2023}},
}