Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.
Solomon O., Huen K., Yousefi P., Küpers LK., González JR., Suderman M., Reese SE., Page CM., Gruzieva O., Rzehak P., Gao L., Bakulski KM., Novoloaca A., Allard C., Pappa I., Llambrich M., Vives M., Jima DD., Kvist T., Baccarelli A., White C., Rezwan FI., Sharp GC., Tindula G., Bergström A., Grote V., Dou JF., Isaevska E., Magnus MC., Corpeleijn E., Perron P., Jaddoe VWV., Nohr EA., Maitre L., Foraster M., Hoyo C., Håberg SE., Lahti J., DeMeo DL., Zhang H., Karmaus W., Kull I., Koletzko B., Feinberg JI., Gagliardi L., Bouchard L., Ramlau-Hansen CH., Tiemeier H., Santorelli G., Maguire RL., Czamara D., Litonjua AA., Langhendries J-P., Plusquin M., Lepeule J., Binder EB., Verduci E., Dwyer T., Carracedo Á., Ferre N., Eskenazi B., Kogevinas M., Nawrot TS., Munthe-Kaas MC., Herceg Z., Relton C., Melén E., Gruszfeld D., Breton C., Fallin MD., Ghantous A., Nystad W., Heude B., Snieder H., Hivert M-F., Felix JF., Sørensen TIA., Bustamante M., Murphy SK., Raikkönen K., Oken E., Holloway JW., Arshad SH., London SJ., Holland N.
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