A Genome-Wide Analysis of Clinical Chorioamnionitis among Preterm Infants

Abstract

Objective: To identify single nucleotide polymorphisms (SNPs) associated with clinical chorioamnionitis among preterm infants.

Study design: We reanalyzed a genome-wide association study (GWAS) from preterm newborns at less than 30 weeks' gestation. Cases and control definitions were determined using administrative records. There were 213 clinical chorioamnionitis cases and 707 clinically uninfected controls. We compared demographic and clinical outcomes of cases and controls. We performed a GWAS and compared the distribution of SNPs from the background genes and from the immunome genes. We used a Wilcoxon's rank-sum test to compare the SNPs normalized odds ratio and used odds ratios and p-values to determine candidate genes.

Results: Infants affected by clinical chorioamnionitis were more likely to have periventricular leukomalacia, high-grade retinopathy, and high-grade intraventricular hemorrhage (IVH). Although a GWAS did not identify SNPs associated with clinical chorioamnionitis at the genome-wide significance level, a direct test on the exonic variants in the human immunome revealed their significant increase of risk in clinical chorioamnionitis.

Conclusion: Among very preterm infants, clinical chorioamnionitis was associated with periventricular leukomalacia, high-grade retinopathy, and IVH. Our analysis of variants in the human immunome indicates an association with clinical chorioamnionitis in very preterm pregnancies.

Figure 1.

Inclusion and exclusion flow sheet to determine eligibility.

Figure 2.

Box plot showing the association between immunome and background single nucleotide polymorphisms (SNPs) in chorioamnionitis. Each red circle represents the normalized odds of SNP outliers. Lower bound of the box represents the 25^th percentile and the upper bound represents the 75^th percentile. The lower and upper caps represent the 5^th and 95^th percentile, respectively. The red line within each box represents the median normalized odds ratio and the dotted red line extended across the plot represents the median of the background exonic region.