Pregnancy is a sensitive period for a developing embryo/fetus where cues from the environment are incorporated into the epigenome where they can have long-term implications. While certain prenatal exposures, like alcohol and smoking, are well known to produce a number of negative health outcomes, they remain the largest cause of preventable birth defects and are relatively understudied considering their prevalence.
By utilizing some powerful epigenomic epidemiology, the talented team from the National Institute of Environmental Health Sciences (NIEHS) who brought us the CpG profile of prenatal exposure to smoking has upped the ante. Now they’ve formed an enormous collaboration with a number of other labs named the International Pregnancy and Childhood Epigenetics (PACE) consortium.
The meta-analysis conducted by the PACE consortium consisted primarily of non-smokers (62%) as well mothers with any level smoking (25%) and those with sustained smoking (13%). Here’s what was found in the cord-blood of 13 cohorts (n=6685) from the US and Europe:
- When compared to non-smokers, 6073 differentially methylated CpGs were associated with prenatal exposure to sustained maternal smoking.
- The most significant CpG was related to the AHRR gene, which is the most significant hit in a number of other studies examining either prenatal exposure to smoking or adult smoking.
- 2,965 of the CpGs identified, which corresponded to 2017 genes, were not previously implicated.
- Several of the identified genes are related to orofacial clefts, asthma, and cancers, and have been implicated in either prenatal or adult exposure to smoking.
- There was also an enrichment for pathways, gene networks, and ontologies related to developmental events.
- Different normalization and cell-type adjustment methods substantially lowered the overall number of CpGs but still produced “robust” results.
- In separate follow-ups on older children (5 cohorts, n= 3187) all the CpGs had at least nominal levels of significance.
- Some of the identified CpGs were associated with altered transcription in select cohorts.
Senior co-author Stephanie London shares, “We already knew that smoking is related to cleft lip and palate, but we don’t know why. Methylation might be somehow involved in the process. I find it kind of amazing when we see these epigenetic signals in newborns, from in utero exposure, lighting up the same genes as an adult’s own cigarette smoking. There’s a lot of overlap. This is a blood-borne exposure to smoking–the fetus isn’t breathing it, but many of the same things are going to be passing through the placenta”.
Go check out this powerful epidemiological study over at The American Journal of Human Genetics, April 2016