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Birth Weight Is Ass...
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Schuermans, ArtMassachusetts General Hospital,Broad Institute
(author)
Birth Weight Is Associated With Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Outcomes in Adulthood
- Article/chapterEnglish2023
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LIBRIS-ID:oai:lup.lub.lu.se:ce0c9de5-4f8c-4c8b-b3a1-48ff1099c060
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https://lup.lub.lu.se/record/ce0c9de5-4f8c-4c8b-b3a1-48ff1099c060URI
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https://doi.org/10.1161/JAHA.123.030220DOI
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Language:English
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Summary in:English
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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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Nakao, TetsushiMassachusetts General Hospital,Broad Institute,Brigham and Women's Hospital / Harvard Medical School
(author)
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Ruan, YunfengMassachusetts General Hospital,Broad Institute
(author)
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Koyama, SatoshiBroad Institute,Massachusetts General Hospital(Swepub:lu)sa2525ko
(author)
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Yu, ZhiMassachusetts General Hospital,Broad Institute
(author)
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Uddin, Md MesbahMassachusetts General Hospital,Broad Institute
(author)
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Haidermota, SaraBroad Institute,Massachusetts General Hospital
(author)
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Hornsby, WhitneyMassachusetts General Hospital,Broad Institute
(author)
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Lewandowski, Adam J.University of Oxford
(author)
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Bick, Alexander G.Vanderbilt University Medical Center
(author)
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Niroula, AbhishekLund University,Lunds universitet,Institutionen för laboratoriemedicin,Medicinska fakulteten,Department of Laboratory Medicine,Faculty of Medicine,Broad Institute,Dana-Farber Cancer Institute(Swepub:lu)med-anu
(author)
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Jaiswal, SiddharthaStanford University School of Medicine
(author)
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Ebert, Benjamin L.Howard Hughes Medical Institute,Dana-Farber Cancer Institute
(author)
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Natarajan, PradeepHarvard Medical School,Massachusetts General Hospital,Broad Institute
(author)
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Honigberg, Michael C.Harvard Medical School,Broad Institute,Massachusetts General Hospital
(author)
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Massachusetts General HospitalBroad Institute
(creator_code:org_t)
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In:Journal of the American Heart Association12:132047-9980
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Schuermans, Art
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Nakao, Tetsushi
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Ruan, Yunfeng
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Koyama, Satoshi
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Yu, Zhi
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Uddin, Md Mesbah
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Haidermota, Sara
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Hornsby, Whitney
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Lewandowski, Ada ...
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Bick, Alexander ...
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Ebert, Benjamin ...
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