Electronic Theses and Dissertations

Yan Shen

Date

2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Epidemiology

Committee Chair

Wilfried Karmaus

Committee Member

Hongmei Zhang

Committee Member

Fawaz Mzayek

Committee Member

Yu Jiang

Abstract

Prior research demonstrated intergenerational effects of maternal risk factors on offspring birth weight. However, only a limited number of studies investigated whether grand-maternal risk factors, i.e. body mass index (BMI) and socioeconomic status (SES), affected grandchilds birth weight (GBW). Besides, it is unknown whether such associations are direct or mediated by maternal risk factors. Grand-maternal smoking during pregnancy was additionally included due to many studies addressing the adverse effect of maternal smoking on birth weight. I used three-generation data from Isle of Wight birth cohort in UK and performed structural equation models (SEM) to assess the associations between grand-maternal risk factors and GBW.First, I evaluated whether the association between grand-maternal BMI and GBW can be mediated by maternal birth weight and BMI in early adulthood. An indirect effect of grand-maternal BMI on increasing GBW was mediated by maternal birth weight and maternal BMI at age 18. The decreasing indirect effect of grand-maternal smoking during pregnancy on GBW was mediated by maternal birth weight and maternal smoking during pregnancy. Next, I evaluated whether the association between grand-maternal SES and GBW can be mediated by maternal birth weight and smoking during pregnancy. There was neither direct nor indirect association between grand-maternal SES and GBW. Finally, I evaluated whether DNA methylation (DNAm) in early adulthood can mediate the associations between grand-maternal BMI and GBW, and between grand-maternal smoking during pregnancy and GBW. Results of screening analyses showed that two CpG sites at cg01481989 and cg13595777 were associated with both grand-maternal BMI and GBW. SEM results showed that maternal DNAm at cg01481989 and cg13595777 at age 18 mediated the positive association between grand-maternal BMI and GBW. The adverse and indirect association between grand-maternal smoking during pregnancy and GBW was mediated by maternal smoking level during pregnancy. The findings regarding the mediating role of maternal DNAm on the association between grand-maternal BMI and GBW should be treated with caution, because replications are required to corroborate these findings.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest

Notes

embargoed

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