The study demonstrates that the apolipoprotein(a) (apo(a)) gene accounts for over 90% of the variation in plasma lipoprotein(a) (Lp(a)) concentrations. Using 48 nuclear Caucasian families, researchers analyzed plasma Lp(a) levels and apo(a) genotypes. They employed pulsed-field gel electrophoresis to distinguish 19 different apo(a) genotypes. The apo(a) gene was found to be the major determinant of plasma Lp(a) levels, with the number of kringle 4 repeats accounting for 69% of the variation. Additional cis-acting sequences at the apo(a) locus contributed the remaining 22%. Siblings sharing identical apo(a) alleles had highly similar Lp(a) levels (r = 0.95), while those sharing no alleles had dissimilar levels (r = -0.23). The apo(a) gene explained 91% of the variance in plasma Lp(a) concentrations. A new apo(a) allele was identified, arising from a de novo mutation in a paternal gamete. The study highlights the significant genetic influence on Lp(a) levels, with the apo(a) gene playing a central role. The findings suggest that factors other than kringle 4 repeats also contribute to Lp(a) variation. The study underscores the importance of the apo(a) gene in determining plasma Lp(a) concentrations and provides insights into the genetic architecture of this trait.The study demonstrates that the apolipoprotein(a) (apo(a)) gene accounts for over 90% of the variation in plasma lipoprotein(a) (Lp(a)) concentrations. Using 48 nuclear Caucasian families, researchers analyzed plasma Lp(a) levels and apo(a) genotypes. They employed pulsed-field gel electrophoresis to distinguish 19 different apo(a) genotypes. The apo(a) gene was found to be the major determinant of plasma Lp(a) levels, with the number of kringle 4 repeats accounting for 69% of the variation. Additional cis-acting sequences at the apo(a) locus contributed the remaining 22%. Siblings sharing identical apo(a) alleles had highly similar Lp(a) levels (r = 0.95), while those sharing no alleles had dissimilar levels (r = -0.23). The apo(a) gene explained 91% of the variance in plasma Lp(a) concentrations. A new apo(a) allele was identified, arising from a de novo mutation in a paternal gamete. The study highlights the significant genetic influence on Lp(a) levels, with the apo(a) gene playing a central role. The findings suggest that factors other than kringle 4 repeats also contribute to Lp(a) variation. The study underscores the importance of the apo(a) gene in determining plasma Lp(a) concentrations and provides insights into the genetic architecture of this trait.