Genetics
Sequencing advances resolve LPA genetic architecture across ancestries, but the Lp(a) receptor stays elusive, review (Curr Opin Lipidol 2026)
Original title: Recent advances in understanding the spectrum of genetic determinants of lipoprotein(a) levels
Review of recent advances in understanding the genetic determinants of Lp(a), a field long limited by the complex repetitive structure of the LPA gene, sparse non-European datasets, and an unclear cellular receptor. Advances in DNA sequencing and bioinformatics now resolve LPA variants and kringle IV type 2 copy number at scale, generating new reference datasets and tools that unlock hidden variation in existing sequencing data. Genetic studies are broadening understanding of Lp(a) regulation across ancestries and improving genetic risk scores, while genome-wide knockout screens are searching for new uptake regulators and receptors, though findings still converge, puzzlingly, on the LDL receptor. The author concludes these advances build a foundation for more accurate, ancestry-inclusive genetic risk assessment and future integrative studies of Lp(a) biology.
Original abstract
Purpose Of Review: Our understanding of the genetic regulation of lipoprotein(a) [Lp(a)] is hindered by the complex structure of the LPA gene, limited non-European datasets and its elusive cellular receptor(s). This review summarizes recent efforts and advances providing new insights on its genetic architecture, variability across ancestries and regulators beyond the LPA gene.
Recent Findings: Impressive advances in DNA sequencing and bioinformatics now resolve LPA variants and kringle IV-type 2 copy number at scale. This provides new reference datasets and enables tools that unlock hidden variation also from already available sequencing datasets. In parallel, genetic studies broaden our understanding of the regulation of Lp(a) across ancestries and improve genetic risk scores. Finally, while recent studies implicate new mechanisms for Lp(a) uptake, upcoming genome-wide gene knockout screens allow comprehensive, agnostic scans for regulators and receptors. Puzzlingly, this still converges on the LDL receptor, whose exact role in Lp(a) uptake remains enigmatic.
Summary: Technological advances establish a foundation for more accurate genetic risk assessment across ancestries. These advances are enhancing our understanding of Lp(a) regulation and build a framework for future integrative genetic studies, which may shed new light on the evolution of the Lp(a) trait, adding important context for its physiological and clinical relevance.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.