Monogenic ALB Variants as Determinants of Severe Hypercholesterolemia: A Population-Based Cohort Study
Authors' conclusion
ALB LoF variants represent a previously underrecognized monogenic cause of elevated LDL-C, with effect sizes slightly less than canonical familial hypercholesterolemia variants.
Study context
- Population
- Adult participants of Geisinger MyCode (Pennsylvania, US) and NIH All of Us biobanks with linked EHR and genetic data155,530 MyCode
- Comparison
- ALB loss-of-function (LoF) variant carriers vs noncarriers
- ALB LoF variantsn = 77
- Outcome
- LDL-C levels (adjusted for lipid-lowering medication use)
Methodological detailsmeta-analysis across cohorts (fixed-effects)
- Meta-analysis across cohorts (fixed-effects)
Pooled result
As reported in the abstract
LDL-C and serum albumin
Increase in LDL-C, mg/dL (95% CI)
ALB LoF carriers vs Noncarriers
38.3(28.2–48.5)
Reduction in serum albumin, g/dL (95% CI)
ALB LoF carriers vs Noncarriers
0.69(0.60–0.78)
- ALB LoF variant carrier frequency
- 1 of 7,289
- Noncarriers: decrease in low-density lipoprotein cholesterol (LDL-C) (mg/dL) per 1 g/dL decrease in serum albumin
- 10.9 (95% CI: 10.4-11.4)
Further pooled results
LDL-C per decile of polygenic score for lower albumin (European ancestry)
- Decrease in LDL-C (mg/dL) per decile
- 0.22 (95% CI: 0.17-0.26)
Original publication
Monogenic ALB Variants as Determinants of Severe Hypercholesterolemia: A Population-Based Cohort Study. J Am Coll Cardiol. Published 13 May 2026. doi:10.
Summarised from the published abstract; every number is checked against it