PROJECT SUMMARY
Pregnancy is an important transition period that parous women (those who have given birth) undergo and it is
linked to changes in risk of various diseases as compared to nulliparous women (those who have never given
birth). The number of completed pregnancies changes the risk of autoimmune disease, Alzheimer's disease,
cancers of the ovary, breast and liver, as well as asthma death later in life. However, it is unknown how these
disease risks are altered by the child-bearing experience. DNA methylation (DNA-m) - the addition of a methyl
group to cytosine in cytosine-phosphate-guanine (CpG) dinucleotides sequences in DNA - has been shown to
be associated with multiple health outcomes later in life, such as atopy, eczema, hypertension, diabetes
mellitus, and cancer. Our preliminary studies have shown that more CpGs (5.6% vs 0.7%) change levels of
methylation during pregnancy (measured between age 18 years and again during pregnancy in women not yet
pregnant at age 18) compared to pre-pregnancy (between ages 10 and 18 years), which may represent a
plausible mechanism for altering post-pregnancy disease risks in parous women if these changes remain after
pregnancy. To better understand the links between methylation changes during pregnancy and parous-related
diseases later in life, we propose to identify pregnancy-related CpGs with significant pre- and post-pregnancy
methylation changes through an epigenome-wide study. In Specific Aim 1, we will identify CpGs with significant
methylation changes in parous women between ages 18 and 26-27 years compared to nulliparous women
over the same time period. Then in Specific Aim 2, we will focus on the CpGs identified in Specific Aim 1 and
test what proportion of them change from age 18 years to pregnancy and remain stable after parturition up to
age 26-27 years. This proposed research has the potential to significantly contribute to 1) the discovery of
biomarkers affected by a healthy pregnancy, 2) a better assessment of the long-term effects of parity on
women in later life, and 3) the future development of epigenetic tools to detect these modified disease risks.
Our collaborative research team is well-positioned to do this work with complementary expertise in genetics
and epigenetics, reproductive epidemiology and (bio)statistics, and clinical medicine. We have a long track
record of successful collaboration investigating DNA methylation changes during critical transition periods,
such as puberty and pregnancy.