An Investigation of the Genomic Architecture of Preterm Birth Susceptibility in Multigravid Nigerian Women: A Genome-Wide Association Approach

Preterm birth has a significant heritable component, yet the genomic architecture of preterm birth susceptibility has been studied predominantly in European and North American populations, leaving the genetic determinants in Nigerian women, whose preterm birth burden is among the world's highest, largely unexplored. This dissertation investigates the genomic architecture of preterm birth susceptibility in multigravid Nigerian women using a genome-wide association study (GWAS) design. A discovery cohort of 600 multigravid women with a history of at least one preterm birth and 600 term-delivery controls was recruited across six geopolitical zones at tertiary hospitals. Genome-wide genotyping was performed using the Illumina Infinium Global Screening Array with West African ancestry reference panels for imputation. Ancestry-stratified association testing, fine mapping, and pathway enrichment analysis were conducted. Seventeen genome-wide significant loci (p < 5 x 10-8) were identified, of which nine replicated in a validation cohort. Three loci were novel, including a variant in the WNT4 gene region specifically associated with preterm birth in the Hausa ethnic subgroup. Pathway analysis implicated inflammatory cytokine signalling, cervical matrix remodelling, and progesterone receptor pathways. Polygenic risk score analysis showed significant discriminatory capacity (AUC 0.71) across the full cohort. The dissertation contributes an original Nigerian-ancestry preterm birth GWAS, advances understanding of population-specific genomic risk architecture, and provides biological targets for future precision prevention research. Keywords: preterm birth, GWAS, genomics, Nigeria, genetic susceptibility