DNA methylation as a potential mediator of the association between prenatal tobacco and alcohol exposure and child neurodevelopment in a South African birth cohort

被引:11
作者
Abrishamcar, Sarina [1 ]
Chen, Junyu [1 ]
Feil, Dakotah [1 ]
Kilanowski, Anna [2 ,3 ,4 ]
Koen, Nastassja [5 ,6 ,7 ]
Vanker, Aneesa [8 ]
Wedderburn, Catherine J. [5 ,8 ,9 ]
Donald, Kirsten A. [5 ,8 ]
Zar, Heather J. [6 ,8 ]
Stein, Dan J. [5 ,6 ,7 ]
Huls, Anke [1 ,10 ]
机构
[1] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA
[2] Inst Epidemiol, Helmholtz Zentrum Munchen German Res Ctr Environm, Neuherberg, Germany
[3] Ludwig Maximilians Univ Munchen, Inst Med Informat Proc Biometry & Epidemiol, Pettenkofer Sch Publ Hlth, Munich, Germany
[4] Univ Munich Med Ctr, Dr Hauner Childrens Hosp, Div Metab & Nutr Med, Munich, Germany
[5] Univ Cape Town, Neurosci Inst, Cape Town, South Africa
[6] Univ Cape Town, South African Med Res Council SAMRC Unit Risk & R, Cape Town, South Africa
[7] Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town, South Africa
[8] Univ Cape Town, Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, Cape Town, South Africa
[9] London Sch Hyg & Trop Med, Dept Clin Res, London, England
[10] Emory Univ, Rollins Sch Publ Hlth, Gangarosa Dept Environm Hlth, Atlanta, GA 30332 USA
基金
美国国家卫生研究院; 英国医学研究理事会; 比尔及梅琳达.盖茨基金会; 英国惠康基金; 新加坡国家研究基金会;
关键词
VESICULAR TRANSPORT DISEASE; MATERNAL CIGARETTE-SMOKING; GENE POLYMORPHISM; PREGNANCY; RISK; SCHIZOPHRENIA; EPIGENETICS; NEWBORNS; PACKAGE; MEMORY;
D O I
10.1038/s41398-022-02195-3
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Prenatal tobacco exposure (PTE) and prenatal alcohol exposure (PAE) have been associated with an increased risk of delayed neurodevelopment in children as well as differential newborn DNA methylation (DNAm). However, the biological mechanisms connecting PTE and PAE, DNAm, and neurodevelopment are largely unknown. Here we aim to determine whether differential DNAm mediates the association between PTE and PAE and neurodevelopment at 6 (N = 112) and 24 months (N = 184) in children from the South African Drakenstein Child Health Study. PTE and PAE were assessed antenatally using urine cotinine measurements and the ASSIST questionnaire, respectively. Cord blood DNAm was measured using the EPIC and 450 K BeadChips. Neurodevelopment (cognitive, language, motor, adaptive behavior, socioemotional) was measured using the Bayley Scales of Infant and Toddler Development, Third Edition. We constructed methylation risk scores (MRS) for PTE and PAE and conducted causal mediation analysis (CMA) with these MRS as mediators. Next, we conducted a high-dimensional mediation analysis to identify individual CpG sites as potential mediators, followed by a CMA to estimate the average causal mediation effects (ACME) and total effect (TE). PTE and PAE were associated with neurodevelopment at 6 but not at 24 months. PTE MRS reached a prediction accuracy (R-2) of 0.23 but did not significantly mediate the association between PTE and neurodevelopment. PAE MRS was not predictive of PAE (R-2 = 0.006). For PTE, 31 CpG sites and eight CpG sites were identified as significant mediators (ACME and TE P < 0.05) for the cognitive and motor domains at 6 months, respectively. For PAE, 16 CpG sites and 1 CpG site were significant mediators for the motor and adaptive behavior domains at 6 months, respectively. Several of the associated genes, including MAD1L1, CAMTA1, and ALDH1A2 have been implicated in neurodevelopmental delay, suggesting that differential DNAm may partly explain the biological mechanisms underlying the relationship between PTE and PAE and child neurodevelopment.
引用
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页数:12
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