Hemophilia Inhibitor Genetics Study
Location(s): South Africa; Argentina; Colombia; Venezuela
The Hemophilia Inhibitor Genetics Study (HIGS) is an international investigation that combines the strengths of family and association studies to identify and confirm relationships between genetic factors and the development of inhibitory antibodies to factor VIII. Data and samples contributed by 44 hemophilia treatment centers in Europe, North America, Latin America, and South Africa. The cohort is composed of brother pairs concordant for a history of inhibitors, or discordant (one with an inhibitor, the other without) and a group on singletons with inhibitors, and their parents. In work recently completed, HIGS was joined by two previously described cohorts – the Hemophilia Growth and Development Study and the Malmö International Brother Study – in the evaluation of a large panel of single nucleotide polymorphisms (SNPs) to identify markers associated with inhibitor history. Currently in progress is a replication and confirmatory step to validate associations observed. Also underway is a Transmission Disequilibrium Test (TDT), a powerful analytic strategy developed by Robert Elston (1998). This test requires two parents and an affected offspring to test for distortions from expectations in the transmission of alleles from each heterozygous parent to the affected child.