Aberrant One-Carbon Metabolism and Ancestral Genetics Underlie Edematous Severe Acute Malnutrition

Authors

• Natasha C Lie
• Yixing Han
• Qing Li
• Aarti Jajoo
• Jared Redmond
• Aparna Haldipur
• Solome Zewdu
• Emilyn Banfield
• Shanker Swaminathan
• Sharon Howell
• Orgen Brown
• Roa Sadat
• Nancy J Hall
• Kwesi Marshall
• Katharina V Schulze
• Thaddaeus May
• Marvin E Reid
• Carolyn Taylor-Bryan
• Mark J Manary
• Indi Trehan
• Mamana Mbiyavanga
• Wisdom A Akurugu
• Colin A McKenzie
• Dhriti Sengupta
• Elizabeth G Atkinson
• Ananyo Choudhury
• Neil A Hanchard

Language

English

Publication Date

10-15-2026

Journal

Nature Communications

DOI

10.1038/s41467-026-74239-x

PMID

42875425

PMCID

PMC13669358

PubMedCentral® Posted Date

10-15-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Edematous severe childhood malnutrition is distinct from the non-edematous form of malnutrition and remains a major cause of under-five mortality. Its etiology remains unclear, although aberrant one-carbon metabolism has emerged as a potential contributor. Here, we assess genetic variants at loci known to influence one-carbon metabolism, and determine their association with edematous malnutrition in Jamaica and Malawi. Six loci show evidence of association, including four related to homocysteine and folate metabolism - AHCYL1, PRICKLE2, GABBR2, and PLD2, with SNPs at the latter three also having direct effects on homocysteine-related metabolites in Mendelian Randomization. Collectively, one-carbon metabolism-related variants were significantly associated with edematous malnutrition (z = 3.2), with population differences linked to a shared East African genetic ancestry and distinct signatures of selection. These findings strengthen evidence implicating aberrant one-carbon metabolism in edematous malnutrition and highlight the utility of cell-free DNA, intra-continental admixture, and population genetics for mapping disease risk.

Keywords

Humans, Polymorphism, Single Nucleotide, Malawi, Severe Acute Malnutrition, Carbon, Genetic Predisposition to Disease, Homocysteine, Child, Preschool, Folic Acid, Male, Mendelian Randomization Analysis, Genetics research, Malnutrition, Medical genomics

Published Open-Access

yes

Recommended Citation

Lie, Natasha C; Han, Yixing; Li, Qing; et al., "Aberrant One-Carbon Metabolism and Ancestral Genetics Underlie Edematous Severe Acute Malnutrition" (2026). Faculty, Staff and Students Publications. 8414.
https://digitalcommons.library.tmc.edu/baylor_docs/8414