Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium.
Edwina H YeungRichard J BiedrzyckiLaura C Gómez HerreraPrachand IssarapuJohn DouIrene Fontes MarquesSohail Rafik MansuriChristian Magnus PageJustin HarbsDennis KhodasevichEric PoiselZhongzheng NiuCatherine AllardEmma CaseyFernanda Morales BersteinGiulia MancanoHannah R ElliottRebecca RichmondYiyan HeJustiina RonkainenSylvain SebertErin M BellGemma SharpSunni L MumfordEnrique F SchistermanGiriraj R ChandakCaroline H D FallSirazul A SahariahMatt J SilverAndrew M PrenticeLuigi BouchardMagnus DomellofChristina WestNina HollandBeckey TrinhBrenda EskenaziLea ZillichStephanie H WittTabea SendCarrie BretonKelly M BakulskiM Daniele FallinRebecca J SchmidtDan J SteinHeather J ZarVincent W V JaddoeJohn WrightRegina GrazulevicieneKristine Bjerve GutzkowJordi SunyerAnke HuelsMartine VrijheidSophia HarlidStephanie LondonMarie-France HivertJanine FelixMariona BustamanteWeihua GuanPublished in: Aging cell (2024)
Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (P FDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (P FDR = 6.92 × 10 -8 ) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (P FDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.
Keyphrases
- dna methylation
- genome wide
- birth weight
- pregnancy outcomes
- gestational age
- gene expression
- high fat diet
- pregnant women
- nk cells
- healthcare
- poor prognosis
- young adults
- physical activity
- mental health
- copy number
- type diabetes
- public health
- preterm birth
- transcription factor
- body mass index
- middle aged
- low birth weight
- community dwelling
- big data
- social media
- weight loss
- human health