A cross-cohort analysis of autosomal DNA methylation sex differences in the term placenta

Biology of Sex Differences

Chaini Konwar¹  Amy M. Inkster²  Wendy P. Robinson²  Victor Yuan²  Allison M. Matthews³  Carolyn J. Brown⁴ 

[1] BC Children’s Hospital Research Institute, 950 W 28th Ave, V6H 3N1, Vancouver, Canada;Centre for Molecular Medicine and Therapeutics, 950 W 28th Ave, V6H 3N1, Vancouver, Canada;BC Children’s Hospital Research Institute, 950 W 28th Ave, V6H 3N1, Vancouver, Canada;Department of Medical Genetics, University of British Columbia, 4500 Oak St, V6H 3N1, Vancouver, Canada;BC Children’s Hospital Research Institute, 950 W 28th Ave, V6H 3N1, Vancouver, Canada;Department of Medical Genetics, University of British Columbia, 4500 Oak St, V6H 3N1, Vancouver, Canada;Centre for Molecular Medicine and Therapeutics, 950 W 28th Ave, V6H 3N1, Vancouver, Canada;Department of Pathology & Laboratory Medicine, University of British Columbia, 2211 Wesbrook Mall, V6T 1Z7, Vancouver, Canada;Department of Medical Genetics, University of British Columbia, 4500 Oak St, V6H 3N1, Vancouver, Canada;

关键词: DNA methylation;    Placenta;    Sex as a biological variable;    Sex differences;    Microarray;    Illumina 450K array;    Epigenetics;    Pregnancy;   

DOI  :  10.1186/s13293-021-00381-4

来源: Springer

【 摘 要 】

BackgroundHuman placental DNA methylation (DNAme) data is a valuable resource for studying sex differences during gestation, as DNAme profiles after delivery reflect the cumulative effects of gene expression patterns and exposures across gestation. Here, we present an analysis of sex differences in autosomal DNAme in the uncomplicated term placenta (n = 343) using the Illumina 450K array.ResultsAt a false discovery rate < 0.05 and a mean sex difference in DNAme beta value of > 0.10, we identified 162 autosomal CpG sites that were differentially methylated by sex and replicated in an independent cohort of samples (n = 293). Several of these differentially methylated CpG sites were part of larger correlated regions of sex differential DNAme. Although global DNAme levels did not differ by sex, the majority of significantly differentially methylated CpGs were more highly methylated in male placentae, the opposite of what is seen in differential methylation analyses of somatic tissues. Patterns of autosomal DNAme at these 162 CpGs were significantly associated with maternal age (in males) and newborn birthweight standard deviation (in females).ConclusionsOur results provide a comprehensive analysis of sex differences in autosomal DNAme in the term human placenta. We report a list of high-confidence autosomal sex-associated differentially methylated CpGs and identify several key features of these loci that suggest their relevance to sex differences observed in normative and complicated pregnancies.

【 授权许可】

CC BY