Genome-wide linkage scan of a pedigree with familial hypercholesterolemia suggests susceptibility loci on chromosomes 3q25-26 and 21q22

PLoS One. 2011;6(10):e24838. doi: 10.1371/journal.pone.0024838. Epub 2011 Oct 14.


Background: Familial hypercholesterolemia (FH) is a heritable disorder that can increase the risk of premature coronary heart disease. Studies suggest there are substantial genetic heterogeneities for different populations. Here we tried to identify novel susceptibility loci for FH in a Chinese pedigree.

Methodology/principal findings: We performed a SNP-based genome-wide linkage scan with the Chinese FH pedigree. Two suggestive linkage loci not previously reported were identified on chromosomes 3q25.1-26.1 (NPL = 9.01, nominal P<0.00001, and simulated occurrence per genome scan = 1.08) and 21q22.3 (NPL = 8.95, nominal P<0.00001, and simulated occurrence per genome scan = 1.26). In the interaction analysis with a trimmed version of the pedigree, we obtained a significantly increased joint LOD score (2.70) compared with that obtained when assuming the two loci uncorrelated, suggesting that more than one locus was involved in this pedigree. Exon screening of two candidate genes ABCG1 and LSS from one of the suggestive region 21q22 didn't report any causative mutations.

Conclusions/significances: These results confirm complex etiologies and suggest new genetic casual factors for the FH disorder. Further study of the two candidate regions is advocated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child, Preschool
  • Chromosomes, Human, Pair 21 / genetics*
  • Chromosomes, Human, Pair 3 / genetics*
  • Female
  • Genetic Linkage*
  • Genetic Loci / genetics
  • Genetic Predisposition to Disease*
  • Genome, Human / genetics
  • Genome-Wide Association Study*
  • Haplotypes / genetics
  • Humans
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / genetics*
  • Hyperlipoproteinemia Type II / pathology
  • Lipids / blood
  • Male
  • Middle Aged
  • Pedigree*
  • Phenotype
  • Sequence Analysis, DNA
  • Young Adult


  • Lipids