Rice T, Laskarzewski P M, Rao D C
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110.
Am J Med Genet. 1992 Nov 1;44(4):399-404. doi: 10.1002/ajmg.1320440402.
Commingling and segregation patterns of fasting plasma glucose (GL) were examined in family data from 5 clinics (Cincinnati, Stanford, Iowa, Minnesota, and Oklahoma) of the Lipid Research Clinics (LRC) family study. In addition to the primary question of whether there was a major gene for GL, a secondary purpose was to investigate the possibility of genetic heterogeneity among the 5 clinics. No statistical support was found for heterogeneity among clinics, either in the commingling of distributions or in the segregation patterns. For the combined clinics sample, both a major effect and a multifactorial component were significant. However, the major effect (accounting for 73% of the variance) was not found to be consistent with a major gene, as the hypothesis of Mendelian transmission was rejected. The most parsimonious model involved equal transmission probabilities, which suggests that the major effect is not transmitted from parents to offspring. Possible sources of this major non-Mendelian effect were explored. The multifactorial component accounted for 10% of the variance in GL levels, and no generational differences were noted. Although our study was unable to provide evidence in favor of a major gene effect, it should be noted that a major gene cannot be firmly refuted. For example, a variety of interactions, such as genotype-dependent age effects, could have masked the transmission probabilities.
在脂质研究临床中心（LRC）家族研究的5个诊所（辛辛那提、斯坦福、爱荷华、明尼苏达和俄克拉荷马）的家族数据中，对空腹血糖（GL）的混合与分离模式进行了研究。除了关于是否存在GL主要基因这一主要问题外，第二个目的是调查这5个诊所之间基因异质性的可能性。无论是在分布的混合还是在分离模式方面，均未发现各诊所之间存在异质性的统计学支持。对于合并后的诊所样本，主要效应和多因素成分均具有显著性。然而，由于孟德尔遗传假设被拒绝，未发现主要效应（占方差的73%）与主要基因一致。最简约的模型涉及相等的传递概率，这表明主要效应并非从父母传递给后代。对这种主要的非孟德尔效应的可能来源进行了探索。多因素成分占GL水平方差的10%，且未观察到代际差异。尽管我们的研究未能提供支持主要基因效应的证据，但应该指出的是，也不能完全排除主要基因的存在。例如，各种相互作用，如基因型依赖的年龄效应，可能掩盖了传递概率。
