Improved Genetic Characterization of Hypercholesterolemia in Latvian Patients with Familial Hypercholesterolemia: A Combined Monogenic and Polygenic Approach Using Whole-Genome Sequencing
2024

Genetic Study of Familial Hypercholesterolemia in Latvian Patients

Sample size: 339 publication 10 minutes Evidence: moderate

Author Information

Author(s): Atava Ivanna, Briviba Monta, Nesterovics Georgijs, Saripo Vita, Gilis Dainus, Meiere Ruta, Terauda Elizabete, Skudrina Gunda, Klovins Janis, Latkovskis Gustavs, Ciccodicola Alfredo

Primary Institution: Latvian Biomedical Research and Study Centre

Hypothesis

Can a combined monogenic and polygenic approach using whole-genome sequencing improve the genetic characterization of familial hypercholesterolemia in Latvian patients?

Conclusion

The study identified unique genetic variants in 23.6% of patients and explained 43.7% of hypercholesterolemia cases through combined genetic analysis.

Supporting Evidence

  • 80 unique pathogenic variants were identified in 23.6% of patients.
  • The LDL-C polygenic risk score was highly discriminative compared to the LPA score.
  • 43.7% of hypercholesterolemia cases were genetically explained through combined analysis.
  • Six novel genetic variants were identified in the study.
  • Patients without monogenic variants had similar LDL-C levels to those with monogenic forms.

Takeaway

This study looked at people in Latvia with high cholesterol to find out what genes might be causing it, and they found some new clues that help explain why some people have this problem.

Methodology

Whole-genome sequencing was performed on 339 patients with familial hypercholesterolemia and 515 controls, analyzing genetic variants and calculating polygenic risk scores.

Potential Biases

Selection bias may have occurred as the study included only severely hypercholesterolemic patients referred to a specialized clinic.

Limitations

The study focused on a predominantly Caucasian population, which may limit the generalizability of the findings to other ethnic groups.

Participant Demographics

The cohort included 132 males (38.9%) with a mean age of 51.5 years, and a control group of 515 individuals with a mean age of 40.0 years.

Statistical Information

P-Value

0.030

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.3390/ijms252413466

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication