Kello, Erin
(2020)
Facial clefting and the Vietnam War: A Study of DNA
Methylation Patterns and Intergenerational Stress.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Changes in DNA methylation patterns have been linked to extreme stress. These patterns are heritable by the next generation. Facial clefting has been linked to changes in methylation patterns affecting craniofacial genes. In this study we explored: 1. If methylation patterns in offspring are associated with maternal exposure to extreme stress 2. If altered methylation patterns are associated with clefting in offspring 3. If the changes preferentially altered craniofacial genes. The present study used peripheral blood samples from 4 cohorts of children. Samples were randomly chosen from a larger group of 505 samples. Group 1 (N=7) have mothers born during the Vietnam war and have CL/P. Group 2 (N=8) have mothers born after the Vietnam war and have CL/P. Group 3 (N=8) have mothers born during the Vietnam war and do not have CL/P. Group 4 (N=8) have mothers born after the Vietnam war and do not have CL/P. We carried out an epigenome wide association study (EWAS) to test the association between DNA methylation pattern, exposure and cleft status, utilizing comparisons between the larger exposed and not exposed cohorts, and cross-wise comparisons between each of the smaller cohorts. Significant results were obtained at the FDR .05 level confirming that overall methylation patterns in children born to mothers who were exposed to war stress and children born to mothers who were not exposed to war stress are different. The affected genes represent an array of core biological functions from cell growth and proliferation to neurological and craniofacial development. The results for the cross-wise comparisons of groups are less conclusive, likely because of the small sample size. However, several probes were significant at the FDR .05 level. The results for the clefts vs. non-cleft groups may have identified novel loci that are associated clefting in this population. The next step in this study is to evaluate the larger group of samples to ascertain if these associations hold.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
8 June 2020 |
| Date Type: |
Publication |
| Defense Date: |
2 March 2020 |
| Approval Date: |
8 June 2020 |
| Submission Date: |
23 March 2020 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
57 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Anthropology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
DNA, methylation, cleft lip and palate, epigenetic, Vietnam War, stress, craniofacial, EWAS |
| Date Deposited: |
08 Jun 2020 16:28 |
| Last Modified: |
08 Jun 2020 16:28 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/38366 |
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