Cord blood transcriptome-wide association study identifying genes associated with metabolic disrupting chemicals and infant growth

Abstract

BACKGROUND AND AIM: Prenatal exposure to metabolic disrupting chemicals (MDCs) has been linked to childhood obesity, however, the underlying mechanism is not clear. The first two years of life are critical for the development of childhood obesity, with adverse consequences including adult obesity, diabetes, and non-communicable diseases. We aimed to elucidate the role of cord blood transcriptomic influence in prenatal MDC-induced increased infant growth. METHODS: Cord blood samples were obtained from 192 Belgian mother-singleton pairs, and mRNA was profiled for gene expression using Agilent Whole Human Genome Microarray 4x44K. A linear regression-based transcriptome-wide association study (TWAS) was performed to identify transcriptomic features associated with prenatal MDCs [including dichlorodiphenyldichloroethylene (p,p'-DDE), polychlorinated biphenyls congener 153 (PCB-153), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS)], measured in cord blood, and with infant growth, defined as body mass index z-score change between birth and 2 years. A triangulation approach, consisting of mediation analysis, pathway enrichment analysis and transcription factor enrichment analysis, was conducted to assess the functional activity of transcriptomics in the relationship between MDCs and infant growth. RESULTS: TWAS identified 521 features associated with infant growth, and 940, 242, 711, 206 features associated with p,p’-DDE, PCB-153, PFOA, PFOS, respectively. Mediation analysis identified 58 genes mediating the indirect effects of MDCs on infant growth. Particularly, IL34 gene expression was found to mediate both p,p’-DDE and PFOA. No overlapping pathways or transcription factors were associated with MDCs and with infant growth. CONCLUSIONS: Mediating effects of certain gene expressions on the associations between MDCs and infant growth were identified. This is the first study to investigate the relationship between prenatal MDCs and infant growth by exploring transcriptomic profiling in cord blood, and the triangulation approach provides new insights into the underlying mechanisms. KEYWORDS: Prenatal exposures, Metabolic disrupting chemicals, Microarray, Infant growth