Mol Genet Genomic Med. 2026 Jul;14(7):e70262. doi: 10.1002/mgg3.70262.
ABSTRACT
BACKGROUND: Genome-wide association studies continue to recruit larger samples, increase resolution, and improve their statistical foundations. These investigations often remain restricted by design to large, outbred populations. This can exclude genetically distinct populations, to whom the genetic insights gained may not apply, and forgoes the benefits that isolated populations can offer to biomedical research. Metabolic Syndrome (MetS) is a collection of highly correlated risk factors that predisposes individuals to type 2 diabetes, cardiovascular disease, and chronic kidney disease. The environmental factors that lead to MetS are well understood, but each person's response to these influences is modulated by their genetics.
METHODS: In this mini-review, we discuss the features of population isolates for mapping disease genes, briefly consider some of the clinical aspects of MetS, and compare the recent contributions to understanding the genetic causes of MetS by population isolates and by large open-population approaches.
RESULTS: Studies in isolated populations have revealed novel genetic associations, including determining causal variants. Isolated populations have also validated and refined associated loci discovered in large, open populations.
CONCLUSION: Much progress has been made uncovering the genetic basis of MetS and related conditions. However, while the field progresses, the definition of the syndrome remains contested, and a comprehensive understanding of MetS genetics remains elusive.
PMID:42411037 | DOI:10.1002/mgg3.70262