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Environmental Factor

Environmental Factor

Your Online Source for NIEHS News

April 2016

NIEHS scientists help form international consortium

NIEHS scientists helped form the international Pregnancy And Childhood Epigenetics consortium, to study effects of early life exposures.

NIEHS scientists played a leading role in forming the Pregnancy And Childhood Epigenetics (PACE) consortium, an international group of researchers using epigenetics to study how environmental exposures in early life affect human disease. Epigenetics refers to modifications to DNA that do not alter the DNA sequence.

PACE grew out of a 2013 meeting organized by Stephanie London, M.D., Dr.P.H., deputy chief of the NIEHS Epidemiology Branch. The meeting brought together scientists who were interested in combining their genetic data from their studies of newborns and children by using a statistical technique known as meta-analysis. Specifically, these scientists are studying genome-wide methylation data using a platform known as Illumina450K. Methylation, or the addition of methyl groups onto DNA, is one form of epigenetic modification.

"Many studies suggest that what a mother is exposed to during pregnancy has an effect on her child’s health years later," London said. "Bringing all of our data together strengthens our ability to find those links."

The PACE approach of combining genotyping data from genome-wide association studies (GWAS) with meta-analysis has been successful. The consortium recently celebrated two milestones — the launch of its website and publication of its first peer-reviewed journal article (see text box).

Setting the PACE for environmental research

PACE has a flexible organization modeled after GWAS consortia such as the 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 participating in one of these other GWAS consortia.

The research conducted by PACE scientists is organized by project. At present, more than 120 scientists working on 24 different studies examine respiratory and allergic conditions, ear infections, and anthropometry, or collection of an individual’s physical measurements. Pregnancy outcomes under study include gestational hypertension and preeclampsia. PACE scientists are also collaborating on several methodological issues involved in analyzing methylation data.


Although London spearheaded PACE, several other epidemiologists from NIEHS are also members of the consortium, including Bonnie Joubert, Ph.D., who took the lead on the meta-analysis and writing for the new paper. Joubert is now a health scientist administrator in the NIEHS Division of Extramural Research and Training. Other NIEHS scientists involved include Zongli Xu, Ph.D.; Jack Taylor, M.D., Ph.D.; Allen Wilcox, M.D., Ph.D.; and Sarah Reese, Ph.D. Tianyuan Wang, Ph.D., a contract scientist for NIEHS, provided bioinformatics assistance.

These researchers are not the only ones helping to make the collaboration a success. PACE boasts a number of former NIEHS postdoctoral and research fellows, including Christina Markunas, Ph.D., at Research Triangle International, and Siri Haberg, M.D., Ph.D., at the National Institute of Public Health in Oslo, Norway.

A number of NIEHS grantees are also part of the PACE team. Two grantees from universities near NIEHS include Cathrine Hoyo, Ph.D., associate professor at North Carolina State University in Raleigh, and Susan Murphy, Ph.D., associate professor at Duke University in Durham.

Regardless of institutional affiliation, PACE scientists are using epigenetics to help improve human health.

Pace publishes first results

The PACE consortium’s first publication appeared online March 31 in the American Journal of Human Genetics.

Using the Illumina450K platform, PACE researchers found more than 6,000 differentially methylated CpG sites, or pairs of the DNA nucleotides cytosine and guanine that exhibit different methylation patterns, in newborns of mothers who smoked during pregnancy. Researchers speculate that some of these epigenetic changes might have effects on development.

Nearly 3,000 of the newly identified CpGs, which corresponded to 2,017 genes, were not previously associated with smoking and methylation in either newborns or adults. Genetic studies have previously implicated some of these genes in orofacial clefts, asthma, and lung and colorectal cancers. Notably, many of these epigenetic signals persist into childhood.

Joubert meta-analyzed the results, which were generated by 13 separate cohorts. She began the work when she was a research fellow in the NIEHS Epidemiology Branch.

Citation: Joubert BR, Felix JF, Yousefi P, Bakulski KM, Just AC, Breton C, Reese S, Markunas CA, Richmond RC, Xu C-J, Kupers LK, Oh SS, Hoyo C, Gruzieva O, Soderhall C, Salas LA, Baiz N, Zhang H, Lepeule J, Ruiz C, Ligthart S, Wang T, Taylor JA, Duijts L, Sharp GC, Jankipersadsing SA, Nilsen RM, Vaez A, Fallin MD, Hu D, Litonjua AA, Fuemmeler BF, Huen K, Kere J, Kull I, Munthe-Kaas MC, Gehring U, Bustamante M, Saurel-Coubizolles MJ, Quraishi BM, Ren J, Tost J, Gonzalez JR, Peters MJ, Haberg SE, Xu Z, van Meurs JB, Gaunt TR, Kerkhof M, Corpeleijn E, Feinberg AP, Eng C, Baccarelli AA, Neelon SEB, Bradman A, Merid K, Bergstrom A, Herceg Z, Hernandez-Vargas H, Brunekreef B, Pinart M, Heude B, Ewart S, Yao J, Lemonnier N, Franco OH Wu MC, Hofman A, McArdle W, Van der Vlies P, Falahi F, Gillman MW, Barcellos LF, Kumar A, Wickman M, Guerra S, Charles M-A, Holloway J, Auffray C, Tiemeier HW, Smith GD, Postma D, Hivert M-F, Eskenazi B, Vrijheid M, Arshad H, Anto JM, Dehghan A, Karmaus W, Annesi-Maesano I, Sunyer J, Ghantous A, Pershagen G, Holland N, Murphy SK, DeMeo DL, Burchard EG, Ladd-Acosta C, Snieder H, Nystad W, Koppelman GH, Relton CL, Jaddoe VWV, Wilcox A, Melen E, London SJ. 2016. DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis. Am J Hum Genet; doi: [Online 31 March 2016].

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