Publication Date



Open access

Embargo Period


Degree Type


Degree Name

Doctor of Philosophy (PHD)


Biochemistry and Molecular Biology (Medicine)

Date of Defense


First Committee Member

Olaf A. Bodamer

Second Committee Member

Ralf Landgraf

Third Committee Member

Stephan Zuchner

Fourth Committee Member

Juan Young

Fifth Committee Member

JoNell E. Potter


Defined as live births prior to the completion of 37 weeks of gestation, preterm birth (PTB) affects up to 13% of all US deliveries. PTB is one of the largest causes of perinatal morbidity and mortality resulting for a large economic burden. With an overall heritability of up to 37%, PTB is a multifactorial condition and is poorly understood. Despite being highly ancestry variable in affectation, few replicable studies have identified variants, transcriptional or epigenetic changes. The objective of this study is to utilize a multi-omics approach in well-characterized SPTB cohorts: exome sequencing in Latin-American infant SPTB cases; and RNA sequencing and methylation genotyping in a white-Caucasian case/control longitudinal cohort. For the Latin-American cohort, I performed a personal genome approach in analyzing the individuals and performing a gene-based analysis method for identifying and prioritizing potentially damaging genes. Many developmental pathways were highly enriched e.g. NRAS signaling pathway by the resulting genes where IP3R was frequent in most pathways. This could elude towards the infants being affected by intrauterine growth restriction (IUGR) and thereby causing SPTB. For the longitudinal cohort taken at 3 time points: gestation, pregnancy, and post-partum, I performed RNA sequencing and genotyping analysis separately in a linear model framework and integrated using Spearman’s rank correlation. Based on 3,408 differentially expressed transcripts and 20,448 differentially methylated positions (both, q < 0.05), I identified eleven candidate regulatory changes. CHIT1 (ρ = -0.69) had the highest inverse correlation between the data types and held most promise in clinical utility. CHIT1 is clinically used to test for decreased levels of -glucocerebrosidase in patients with Gaucher’s disease and a role in increased immune responses. Therefore, CHIT1 has ease in clinical use for the potential diagnosis of mothers during pregnancy for PTB. Upon integrating between the results of cohort via network analysis, I observed trends in a dysregulation in immunological genes supported by the observation of hub genes such MMP-8, IL-6 and NIK (MAP3K12). To the best of my knowledge, the multi-omics approach towards understanding the etiology of PTB is the first reported in current literature. The genes identified in this study could therefore be used towards potential development of therapeutic targets in PTB.


Preterm; Genetics; Epidemiology; Perinatology; Genomics