Pregnancy And Childhood Epigenetics (PACE)
The Pregnancy And Childhood Epigenetics (PACE) consortium is comprised of researchers at NIEHS and around the world who are interested in studying the early life environmental impacts on human disease using epigenetics. Epigenetics refers to modifications to DNA that do not alter the DNA sequence.
Pregnancy and early life are believed to be periods when environmental impacts on the epigenome can have long-lasting implications on health. Experimental models have shown that some in utero exposures can impact offspring methylation, leading to altered phenotypes. DNA methylation is the mostly commonly studied epigenetic modification in humans.
The advent of a platform to measure methylation with reasonable epigenome wide coverage, the Illumina HumanMethylation 450K (Illumina450K), has facilitated population studies of effects of in utero exposures on children, as well as the impact of methylation patterns on subsequent disease. An early paper using this platform identified replicable methylation signals in newborns from maternal smoking in pregnancy and suggested the promise of this approach for looking at other in utero exposures (Joubert et al., 2012).
The consortium approach of combining studies with meta-analysis to achieve greater power for novel discovery had been very successful with genome wide association studies (GWAS) of genotyping data and provided a model for other types of genomic data, such as methylation.
PACE grew out of a 2013 meeting organized by NIEHS Epidemiology Branch Senior Investigator and PACE researcher, Stephanie London, M.D., Dr.P.H. The meeting brought together scientists from newborn or child cohorts with Illumina 450K genome wide methylation data interested in combining data using meta-analysis.
PACE has a flexible organization modeled after GWAS consortia including Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), Early Growth Genetics (EGG), and EArly Genetics and Lifecourse Epidemiology (EAGLE). Many PACE investigators were already participants in one of these GWAS consortia.
The scientific work in the PACE consortium is driven by the researchers and organized by project. Different cohorts participate in each PACE project depending on their data, time, priorities, and interest.
PACE has a bottom-up, researcher-driven organization based on the following principles:
- scientific excellence
- collaborative spirit
- maximizing opportunities for leadership across cohorts
- “no surprises"
- mutual trust and confidentiality
- open communication
- promotion of careers of junior investigators and fellows
Cohorts with methylation data on newborns or children generated using either the Illumina 450K or Illumina EPIC chip are welcome to join. When individuals contact us about having their cohorts join PACE, we ask that individual researchers sign a confidentiality statement agreeing to keep all information exchanged during calls, email, or at in-person meetings, confidential. We also send the PACE principles, so they can decide whether they are compatible with their individual and cohort needs before joining. The PACE Consortium is described in detail in a recent publication.