Relative predispositional effects (RPEs) of marker alleles with disease: HLA-DR alleles and Graves disease.
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.
Payami
H
H
Department of Medical Genetics, Oregon Health Sciences University, Portland 97201.
Joe
S
S
Farid
N R
NR
Stenszky
V
V
Chan
S H
SH
Yeo
P P
PP
Cheah
J S
JS
Thomson
G
G
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
D005819:Genetic Markers; D006684:HLA-DR Antigens