Falk C T, Rubinstein P
Ann Hum Genet. 1980 Jan;43(3):295-301. doi: 10.1111/j.1469-1809.1980.tb01562.x.
We have examined the numerical properties of relative risk (RR) estimates under the conditions of gene frequency and genetic association (delta) that generally obtain for the different HLA loci. It is found that significant RR may be created solely by the existence of positive delta between the disease susceptibility gene and a specific allele at the marker (e.g. HLA) locus. It is shown further, that the value of RR is strongly affected by the gene frequencies and not only by the corresponding delta. If positive delta exists between one disease susceptibility gene and two HLA haplotypes, the RR estimates will usually be highest for the corresponding heterozygote, intermediate for the two homozygotes and lowest for the other carrier phenotypes. This model was found to be perfectly compatible with the situation encountered in the case of juvenile diabetes mellitus and shows that 'overdominance' is not required to account for the excessive RR found in some populations for certain HLA heterozygous classes.
我们研究了在基因频率和遗传关联（δ）条件下相对风险（RR）估计值的数值特性，这些条件通常适用于不同的HLA位点。结果发现，疾病易感基因与标记（如HLA）位点的特定等位基因之间存在正δ，就可能产生显著的RR。进一步表明，RR值不仅受相应δ的强烈影响，还受基因频率的强烈影响。如果一个疾病易感基因与两个HLA单倍型之间存在正δ，那么相应杂合子的RR估计值通常最高，两个纯合子的RR估计值居中，其他携带者表型的RR估计值最低。该模型与青少年糖尿病病例中遇到的情况完全相符，表明在某些人群中某些HLA杂合类别的RR过高，并不需要“超显性”来解释。
