Aberrant one-carbon metabolism and ancestral genetics underlie edematous severe acute malnutrition.

Genetic variants related to homocysteine and folate metabolism are significantly associated with edematous severe childhood malnutrition, with a z-score of 3.2.

• Why it matters: Understanding the genetic and metabolic factors underlying edematous malnutrition is crucial because its causes remain unclear and it is a major contributor to under-five mortality.
• What they did: The study examined six genetic loci known to influence one-carbon metabolism in children from Jamaica and Malawi, identifying four related to homocysteine and folate pathways, with some variants affecting homocysteine metabolites through Mendelian Randomization.
• The result: Findings suggest that aberrant one-carbon metabolism, linked to East African ancestry and selection signatures, may contribute to edematous malnutrition, emphasizing the role of population genetics and intra-continental admixture in disease risk mapping.