DNA methylation abundantly associates with fetal alcohol spectrum disorder and its subphenotypes

被引:27
作者
Cobben, Jan Maarten [1 ]
Krzyzewska, Izabela M. [2 ]
Venema, Andrea [2 ]
Mul, Adri N. [2 ]
Polstra, Abeltje [2 ]
Postma, Alex, V [2 ,3 ]
Smigiel, Robert [4 ]
Pesz, Karolina [5 ]
Niklinski, Jacek [6 ]
Chomczyk, Monika A. [6 ]
Henneman, Peter [3 ]
Mannens, Marcel M. A. M. [3 ]
机构
[1] Amsterdam Univ Med Ctr, Emma Childrens Hosp, Dept Pediat, AMC, Amsterdam, Netherlands
[2] Amsterdam Univ Med Ctr, Genome Diagnost Lab, Dept Clin Genet, AMC, Amsterdam, Netherlands
[3] Amsterdam Univ Med Ctr, Dept Anat Embryol & Physiol, AMC, Amsterdam, Netherlands
[4] Med Univ Wroclaw, Dept Pediat & Rare Disorders, Wroclaw, Poland
[5] Med Univ Wroclaw, Dept Genet, Wroclaw, Poland
[6] Med Univ Bialystok, Dept Mol Biol, Bialystok, Poland
关键词
450K; DNA-methylation; epigenetic; fetal alcohol spectrum disorder; genome-wide; WIDE ASSOCIATION; SONIC HEDGEHOG; PREVALENCE; EXPOSURE; DIAGNOSIS; ETHANOL; EPIGENETICS; PREGNANCY; GENETICS; CHILDREN;
D O I
10.2217/epi-2018-0221
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Aim: Fetal alcohol spectrum disorder (FASD) involves prenatal growth delay, impaired facial and CNS development and causes severe clinical, social-economic burdens. Here, we aim to detect DNA-methylation aberrations associated with FASD and potential FASD diagnostic and prognostic biomarkers. Patients & methods: The FASD diagnosis was established according to golden-standard protocols in a discovery and independent replication cohort. Genome-wide differential methylation association and replication analyses were performed. Results: We identified several loci that were robustly associated with FASD or one of its sub phenotypes. Our findings were evaluated using previously reported genome-wide surveys. Conclusion: We have detected robust FASD associated differentially methylated positions and differentially methylated regions for FASD in general and for FASD subphenotypes, in other words on growth delay, impaired facial and CNS development.
引用
收藏
页码:767 / 785
页数:19
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