Discovering the Origins of Addiction by Haplotype Analysis

• Activity Number: 2
• Type: Invited
• Date/Time: Sunday, August 11, 2002 : 2:00 PM to 3:50 PM
• Sponsor: National Institue on Drug Abuse-NIH
• Author(s): Bernie Devlin*+ and Howard Seltman and Kathryn Roeder
• Affiliation(s): University of Pittsburgh and Carnegie Mellon University and Carnegie Mellon University
• Keywords: genetics ; association ; evolution ; case control ; complex disease

Abstract

To study complex disease, geneticists typically evaluate multiple markers from known chromosomal regions. For a set of markers on a single chromosome, the ordered string of alleles defines a haplotype. An excess of certain haplotypes in affected versus unaffected individuals indicates the presence of a disease locus in the region defined by the haplotype. While single-marker association can pinpoint a liability gene, associations based on haplotypes can be more powerful. Yet, because the number of possible haplotypes increases quickly with the number of alleles, it is unclear, a priori, whether single-locus or haplotype-based approaches are best. Ideally, there would be some way of focusing tests on particular haplotypes or sets of haplotypes. We have been investigating a method known as Measured Haplotype Analysis (MHA), which groups haplotypes based on evolutionary relationships. The evolutionary relationships produce a limited set of hypothesis tests and increase the interpretability of these tests. We will describe both family-based and case-control association tests within the framework of MHA. We illustrate these methods with data from the Center for Education and Drug Abuse.