A genome-wide association study of neonatal metabolites

Abstract

SummaryThe hereditary component significantly influences the concentration of metabolites in adults. Nevertheless, the precise influence of genetic factors on neonatal metabolites remains uncertain. To bridge this gap, we employed genotype imputation techniques on large-scale low-pass genome data obtained from non-invasive prenatal testing. Subsequently, we conducted association studies on a total of 75 metabolic components in neonates. The study identified a total 17 previous reported associations and 13 novel discovered associations between single nucleotide polymorphisms and metabolic components. These associations were initially found in the discovery cohort (8,744 participants) and subsequently confirmed in a replication cohort (19,041 participants). The average heritability of metabolic components was calculated to be 76.2%, with a range of 69-78.8%. The aforementioned findings offer valuable insights pertaining to the genetic architecture of neonatal metabolism.In BriefLarge-scale genomes of maternal non-invasive prenatal testing provide insights into the genetic contribution to neonatal metabolism.HighlightsGWAS of 27,785 low-pass genomes revealed 13 novel associations of neonatal metabolic components.Estimated an average of 76.2% heritability of neonatal metabolic components and showed the individual concentration can be accurately predicted from polygenic risk scores.A total of 17 established relationships have been observed, providing evidence that maternal genomes can be utilized in neonatal metabolite GWAS.

Utilizing Non-Invasive Prenatal Test Sequencing Data Resource for Human Genetic Investigation

“…Of notable importance is our exploration of the genetic basis underlying common pregnancy disorders, such as gestational diabetes 18,22 and gestational thrombocytopenia 23 , particularly in the underrepresented Chinese population. Furthermore, we have garnered insights into the genetic architecture underpinning molecular phenotypes, including maternal 24 and newborn metabolites 25 .…”

“…We conducted a comparison of genetic effects for a combined total of 53 loci significantly associated with maternal metabolites 24 and 30 loci significantly associated with neonate metabolites 25 . These loci were identified in independent sets of individuals assessed with different sequencing platforms.…”

“…We conducted a comparison of genetic effects for a combined total of 53 loci significantly associated with maternal metabolites 24 and 30 loci significantly associated with neonate metabolites 25 .…”