A trio family study showing association of the lymphotoxin-alpha N26 (804A) allele with coronary artery disease

Eur J Hum Genet. 2004 Sep;12(9):770-4. doi: 10.1038/sj.ejhg.5201244.


Family-based studies to map susceptibility genes through linkage disequilibrium have been successful in early-onset diseases where parental-proband trios are readily collected, but are believed to be unworkable for late-onset diseases such as coronary artery disease (CAD). PROCARDIS is a European multicentre study that was designed to identify susceptibility genes for CAD. We have tested the transmission of a putatively functional allele, lymphotoxin-alpha N26 (804A), in more than 400 PROCARDIS trio families. The present study demonstrates association of this allele with CAD in white Europeans, a different ethnic group with a heavier CAD burden than the Japanese in which the association was initially identified, which suggests a broad relevance to CAD susceptibility. The practicalities of implementing a trio-family design for late-onset diseases are discussed.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Coronary Artery Disease / genetics*
  • DNA Primers
  • European Continental Ancestry Group
  • Family
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Likelihood Functions
  • Linkage Disequilibrium*
  • Lymphotoxin-alpha / genetics*
  • Mass Spectrometry
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Research Design


  • DNA Primers
  • Lymphotoxin-alpha