Associations of DNA Methylation Mortality Risk Markers with Congenital Microcephaly from Zika Virus: A Study of Brazilian Children Less than 4 Years of Age

• DOI: 10.1093/tropej/fmab020
• Publication Date: 2021-03-11T20:10:31Z
• Authors: Jamaji C Nwanaji-...; Lars Van Der Laan; Elorm F Avakame; Kristan A Scott; Heather H Burris; Andres Cardenas
• Keywords: Microcephaly; Zika Virus; Etiology

ABSTRACT Background Zika virus (ZIKV)-associated congenital microcephaly is an important contributor to pediatric death, and more robust mortality risk metrics are needed help guide life plans clinical decision making for these patients. Although common etiologies of adult differ, early health can impact outcomes—potentially through DNA methylation. Hence, in this pilot study, we take step identifying by examining associations ZIKV infection associated with existing methylation-based biomarkers: GrimAge Zhang’s score (ZMS). Methods Mortality measures were calculated from previously published HumanMethylationEPIC BeadChip data 44 Brazilian children aged 5–40 months (18 ZIKV-associated microcephaly; 7 normocephalic, exposed utero; 19 unexposed controls). We used linear models adjusted chronological age, sex, methylation batch white blood cell proportions evaluate marker relationships. Results observed significant decreases GrimAge-component plasminogen activator inhibitor-1 [PAI-1; β = −2453.06 pg/ml, 95% confidence interval (CI) −3652.96, −1253.16, p 0.0002], ZMS-site cg14975410 (β −0.06, CI −0.09, −0.03, 0.0003) among compared controls. PAI-1 −2448.70 −4384.45, −512.95, 0.01) 0.01, −0.04, 0.06, 0.64) results comparisons ZIKV-exposed controls not statistically significant. Conclusion Our suggest that elements previously-identified epigenetic markers microcephaly, a known risk. These findings may provide insights efforts aimed at developing markers.