Genetic and clinical determinants of neonatal jaundice and growth patterns in the Qingdao birth cohort: A genome-wide association study

TL;DR

This study identifies genetic variants linked to neonatal jaundice and growth patterns in East Asian newborns, offering insights for prenatal screening and early health monitoring.

Contribution

The study reports novel missense mutations and genetic associations specific to East Asian populations, expanding molecular marker databases for neonatal health.

Findings

778 SNPs across 120 genes were significantly associated with neonatal health and growth indicators.

Three novel missense mutations were linked to jaundice resolution and birth weight.

UGT1A and ATP7 genes showed strong associations with jaundice and birth weight, respectively.

Abstract

Neonatal jaundice and early growth patterns are important indicators of early health, and genetic as well as clinical factors are known to influence these traits. However, evidence from East Asian newborns is still limited.

This study presents a genome-wide association study (GWAS) investigating genetic determinants of Healthy Newborn Growth Indicators (HNGI), with a focus on neonatal jaundice (JAU), jaundice resolution (JAUR), birth weight (BW), and growth metrics (weight, height, BMI) measured within 90–105 days after birth. Our analysis identified 778 single-nucleotide polymorphisms (SNPs) across 120 genes significantly associated with HNGI. Among these associated variants, we found 12 missense mutations, seven of which are novel. The most significant association signal was for rs4148323 (P = 2.3 × 10−18) within the UGT1A gene locus, a well-established variant for JAU. Additionally, we discovered three novel missense mutations associated with JAU and JAUR. For BW, a novel missense mutation, rs148399850 (P = 2.3 × 10−8), was identified in the ATP7 gene, suggesting ATP7 as a potential functional regulator of birth weight. Analysis of allele frequency distributions across global and Chinese populations revealed distinct patterns of genetic diversity. Functional enrichment analysis of the candidate genes highlighted 18 genes significantly involved in 14 essential metabolic pathways related to growth and development. Furthermore, an analysis of clinical risk factors using data from the Biobank Japan (BBJ) demonstrated significant influences of various clinical conditions on HNGI.

This comprehensive analysis of newborns from the Qingdao cohort provides critical data for expanding molecular marker databases for prenatal screening, offering early warnings for jaundice, and guiding the healthy growth of newborns.

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