title: Relative predispositional effects (RPEs) of marker alleles with disease: HLA-DR alleles and Graves disease.
abstract: 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.
authors.affiliation: Department of Medical Genetics, Oregon Health Sciences University, Portland 97201.
authors.forename: H
authors.initials: H
authors.lastname: Payami
authors.forename: S
authors.initials: S
authors.lastname: Joe
authors.forename: N R
authors.initials: NR
authors.lastname: Farid
authors.forename: V
authors.initials: V
authors.lastname: Stenszky
authors.forename: S H
authors.initials: SH
authors.lastname: Chan
authors.forename: P P
authors.initials: PP
authors.lastname: Yeo
authors.forename: J S
authors.initials: JS
authors.lastname: Cheah
authors.forename: G
authors.initials: G
authors.lastname: Thomson
mesh_terms: D000483:Alleles; D005128:Eye Diseases / Q000150:complications / Q000235:genetics / Q000276:immunology; D006580:Genetic Carrier Screening; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000150:complications / Q000235:genetics* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D009523:Newfoundland and Labrador
chemical_list: D005819:Genetic Markers; D006684:HLA-DR Antigens