In 27,308 Singapore Chinese Health Study participants, genome-wide and transcriptome-wide analyses validated 10 blood pressure loci, identified an East Asian-specific COL21A1 splice donor variant associated with pulse pressure, prioritized FGF5 (kidney cortex) and ENPEP (pituitary) as regulatory genes, and linked the blood pressure-lowering ENPEP allele to reduced incident diabetes risk, partly mediated through mean arterial pressure.
Genome-wide analyses in the Singapore Chinese Health Study validated 10 known blood pressure loci across five blood pressure traits.
An East Asian-specific splice donor variant in COL21A1 (rs149344559) was associated with pulse pressure.
Integrative transcriptome-wide, colocalization and fine-mapping analyses prioritized FGF5 in kidney cortex and ENPEP in pituitary tissue as candidate regulatory genes for blood pressure.
The blood pressure-lowering allele at ENPEP (T allele, rs1879056) was associated with reduced risk of incident diabetes.
About 20.1% of the genetic association between the ENPEP variant and diabetes was mediated through mean arterial pressure.
The study concludes that ENPEP-mediated dysfunction links blood pressure genetics to diabetes risk and that tissue-specific regulatory pathways underlie blood pressure variation in East Asian people.
This study looked at the genetic basis of blood pressure in more than 27,000 Chinese adults in Singapore. The researchers scanned the genome for variants linked to five blood pressure measures, including hypertension, systolic and diastolic pressure, mean arterial pressure and pulse pressure. They confirmed 10 known blood pressure regions and found a new variant in the COL21A1 gene, seen specifically in East Asian people, that was associated with pulse pressure. The team also combined the genetic data with gene activity data from 49 tissues to work out which genes are likely responsible. This pointed to FGF5 in the kidney and ENPEP in the pituitary gland. A version of ENPEP that lowers blood pressure was also linked to a lower chance of developing diabetes over time. Around one fifth of that link seemed to operate through blood pressure itself, which suggests that other biological routes also contribute. This research suggests that hypertension and diabetes may share some genetic mechanisms, and it adds to knowledge of blood pressure genetics in East Asian populations, who are less represented in genetic studies. The findings are about genetic associations and do not by themselves show how to prevent or treat either condition, and further work would be needed to confirm the biological roles of these genes.
Lau Z, Chang X, Sim K, Wu H, Naaz A, Muniasamy U, et al.. (2026). Integrative Genomic Analyses Identify Collagen Type XXI Alpha 1 Chain and ENPEP-Fibroblast Growth Factor 5 Regulatory Pathways for Blood Pressure Variation in East Asian People.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.126.052309