Relative predispositional effects (RPEs) of marker alleles with disease: HLA-DR alleles and Graves disease

Am J Hum Genet. 1989 Oct;45(4):541-6.


A method is described to reveal the relative predispositional effects (RPEs) (predisposing, protective, or neutral) of the HLA alleles or of any other marker system that is associated with a disease. When the disease is associated with two or more alleles of a locus, the RPE method identifies the associations sequentially according to their strength; thus the problem that a strong association with one allele can create misleading deviations in the frequencies of other alleles is alleviated. Using this method, we have examined the relative effects of HLA-DR alleles in susceptibility to Graves disease in the Caucasian population. The well-established positive association with DR3 was confirmed as the strongest effect. In addition, a negative association was found between DR5 and Graves disease. The reduced frequency of DR5 among patients is statistically significant and is not a result of the increase in DR3. Finally, when patients were divided according to the presence or absence of eye disease, the latter showed a significant increase in the frequency of DR4. With family data, linkage to HLA of Graves disease was established in both Caucasian and Chinese families by the sib-pair method.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Eye Diseases / complications
  • Eye Diseases / genetics
  • Eye Diseases / immunology
  • Genetic Carrier Screening
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Graves Disease / complications
  • Graves Disease / genetics*
  • Graves Disease / immunology
  • HLA-DR Antigens / genetics*
  • Humans
  • Newfoundland and Labrador


  • Genetic Markers
  • HLA-DR Antigens