Nucleated red blood cells explain most of the association between DNA methylation and gestational age

被引：7

作者：

Haftorn, Kristine L. ^{[1
,2
]}

Denault, William R. P. ^{[1
,3
]}

Lee, Yunsung ^{[1
]}

Page, Christian M. ^{[1
,4
]}

Romanowska, Julia ^{[1
,5
]}

Lyle, Robert ^{[1
,6
,7
]}

Naess, Oyvind E. ^{[2
,8
]}

Kristjansson, Dana ^{[1
,9
]}

Magnus, Per M. ^{[1
]}

Haberg, Siri E. ^{[1
]}

Bohlin, Jon ^{[1
,10
]}

Jugessur, Astanand ^{[1
,5
]}

机构：

[1] Norwegian Inst Publ Hlth, Ctr Fertil & Hlth, Oslo, Norway

[2] Univ Oslo, Inst Hlth & Soc, Oslo, Norway

[3] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[4] Norwegian Inst Publ Hlth, Dept Phys Hlth & Ageing, Div Mental & Phys Hlth, Oslo, Norway

[5] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway

[6] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway

[7] Univ Oslo, Oslo, Norway

[8] Norwegian Inst Publ Hlth, Div Mental & Phys Hlth, Oslo, Norway

[9] Norwegian Inst Publ Hlth, Dept Genet & Bioinformat, Oslo, Norway

[10] Norwegian Inst Publ Hlth, Dept Infect Dis Epidemiol & Modelling, Div Infect Control & Environm Hlth, Oslo, Norway

来源：

COMMUNICATIONS BIOLOGY | 2023年 / 6卷 / 01期

基金：

美国国家卫生研究院;

关键词：

GLUCOCORTICOID-RECEPTOR; STRESS ERYTHROPOIESIS; ERYTHROID PROGENITORS; NORWEGIAN MOTHER; WIDE ASSOCIATION; BIRTH-WEIGHT; IDENTIFICATION; EXPRESSION; DIFFERENTIATION; DECONVOLUTION;

D O I：

10.1038/s42003-023-04584-w

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Determining if specific cell type(s) are responsible for an association between DNA methylation (DNAm) and a given phenotype is important for understanding the biological mechanisms underlying the association. Our EWAS of gestational age (GA) in 953 newborns from the Norwegian MoBa study identified 13,660 CpGs significantly associated with GA (p(Bonferroni)<0.05) after adjustment for cell type composition. When the CellDMC algorithm was applied to explore cell-type specific effects, 2,330 CpGs were significantly associated with GA, mostly in nucleated red blood cells [nRBCs; n = 2,030 (87%)]. Similar patterns were found in another dataset based on a different array and when applying an alternative algorithm to CellDMC called Tensor Composition Analysis (TCA). Our findings point to nRBCs as the main cell type driving the DNAm-GA association, implicating an epigenetic signature of erythropoiesis as a likely mechanism. They also explain the poor correlation observed between epigenetic age clocks for newborns and those for adults. CpG sites associated with gestational age are predominantly found in nucleated red blood cells, which point to an epigenetic signature of erythropoiesis as being partly responsible for this association.

引用

页数：11

共 87 条

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