Meta-Analysis of Epigenome-Wide Association Studies in Newborns and Children Show Widespread Sex Differences in Blood DNA Methylation

Details

• Personal Author:
  Allard C ; Baccarelli A ; Bakulski KM ; Bergström A ; Binder EB ; Bouchard L ; Breton C ; Bustamante M ; Carracedo Á ; Corpeleijn E ; Czamara D ; DeMeo DL ; Dou JF ; Dwyer T ; Eskenazi B ; Fallin MD ; Feinberg JI ; Felix JF ; Ferre N ; Foraster M ; Gagliardi L ; Gao L ; Ghantous A ; González JR ; Grote V ; Gruszfeld D ; Gruzieva O ; Håberg SE ; Herceg Z ; Heude B ; Hivert M-F ; Holloway JW ; Hoyo C ; Huen K ; Isaevska E ; Jaddoe VWV ; Jima DD ; Karmaus W ; Kogevinas M ; Koletzko B ; Kull I ; Küpers LK ; Kvist T ; Lahti J ; Langhendries J-P ; Lepeule J ; Litonjua AA ; Llambrich M ; Magnus MC ; Maguire RL ; Maitre L ; Melén E ; Munthe-Kaas MC ; Murphy SK ; Nawrot TS ; Nohr EA ; Novoloaca A ; Nystad W ; Oken E ; Page CM ; Pappa I ; Perron P ; Plusquin M ; Raikkönen K ; Ramlau-Hansen CH ; Reese SE ; Relton C ; Rezwan FI ; Rzehak P ; Santorelli G ; Sharp GC ; Snieder H ; Solomon O ; Sørensen TIA ; Suderman M ; Tiemeier H ; Tindula G ; Verduci E ; Vives M ; White C ; Yousefi P ; Zhang H
• Description:
  Background: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. Methods: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268). Results: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10-7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10-6) in older children and had methylation differences in the same direction. Conclusions: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Epidemiology Genetics Occupational Health Pregnancy Safety Sex Characteristics
• Keywords:
  Author Keywords: DNA Methylation Children Cohort Studies Cord Blood DNA Damage EWAS Genomics Sex Sex Factors
• ISSN:
  1383-5742
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Georgia ; Maryland ; Massachusetts ; Michigan ; New York ; North Carolina ; OSHA Region 1 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 9 ; Tennessee
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  789
• NIOSHTIC Number:
  nn:20070622
• Citation:
  Mutat Res Rev Mutat Res 2022 Jan; 789:108415
• Contact Point Address:
  Karen Huen, School of Public Health, UC Berkeley, 2121 Berkeley Way, CA 94720, USA
• Email:
  khuen@berkeley.edu
• Federal Fiscal Year:
  2022
• Performing Organization:
  University of Michigan, Ann Arbor
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Mutation Research. Reviews in Mutation Research
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fa9554e5b1a99aef00a9820b3cabbcd0154f8fc7b79c00c3141d09cede37bab286e02072f9db49655699312c5034e3d3b911778d2756564b3d32d8819d6c7a56
• Download URL:
  https://stacks.cdc.gov/view/cdc/208801/cdc_208801_DS1.pdf
• File Type:
  [PDF - 3.24 MB ]