病率就可以得出阈值距离均数有几个标准差,这只要查阅正态分布表 即可(表6-2)。易患性正态分布曲线右侧尾部的面积代表发病率。例 如,冠心病的群体患病率为2.3%~25%,其阈值与易患性平均值距 离约2δ;而先天性畸形足的群体患病率仅为0.13%,其阈值与易患性 平均值距离约3δ。 可见,一种多基因病的易患性的平均值与阈值越近,表明易患性 高阈值低,群体患病率高;相反,易患性的平均值与阈值越远,表明 易患性低阈值高,群体患病率低(图6-6)。 图66易患性的平均值和阈值距离与患病率关系 Characteristics of Multifactorial Inheritance 1. Although the disorder is obviously familial, there is no distinctive pattern of inheritance within a single family 2.The risk to first-degree relatives, determined from family studies, is approximately the square root of the population risk As a consequence, the lower the population incidence, the greater the relative increase in risk for first-degree relatives. However only rather large differences in population frequency make an appreciable difference to recurrencerisk 3.The risk is sharp ly lower for second-degree than for first-degree relatives, but it declines less rapidly for more remote relatives This characteristic distinguishes multifactorial inheritance from autosomal dominant inheritance, in which the risk drops by half with each step of more distant relationship. It is also different from the autosomal recessive pattern, in which virtually no relatives other than sibs are at risk 4.The recurrence risk is higher when more than one family member is
6 病率就可以得出阈值距离均数有几个标准差，这只要查阅正态分布表 即可（表 6-2）。易患性正态分布曲线右侧尾部的面积代表发病率。例 如，冠心病的群体患病率为 2.3％～2.5%，其阈值与易患性平均值距 离约 2；而先天性畸形足的群体患病率仅为 0.13％，其阈值与易患性 平均值距离约 3。 可见，一种多基因病的易患性的平均值与阈值越近，表明易患性 高阈值低，群体患病率高；相反，易患性的平均值与阈值越远，表明 易患性低阈值高，群体患病率低（图 6-6）。 图 6-6 易患性的平均值和阈值距离与患病率关系 Characteristics of Multifactorial Inheritance 1.Although the disorder is obviously familial, there is no distinctive pattern of inheritance within a single family. 2.The risk to first-degree relatives, determined from family studies, is approximately the square root of the population risk. As a consequence, the lower the population incidence, the greater the relative increase in risk for first-degree relatives. However, only rather large differences in population frequency make an appreciable difference to recurrence risk. 3.The risk is sharply lower for second-degree than for first-degree relatives, but it declines less rapidly for more remote relatives. This characteristic distinguishes multifactorial inheritance from autosomal dominant inheritance, in which the risk drops by half with each step of more distant relationship. It is also different from the autosomal recessive pattern, in which virtually no relatives other than sibs are at risk. 4.The recurrence risk is higher when more than one family member is
Multiple cases suggest that the liability is high in that particula family. In contrast, for single-gene traits the risk to the next child remains unchanged even after two three or more affected children have een born 5.The more severe the malformation, the greater therecurrence risk More severely affected patients, and their relatives, have greater 6. If a multifactorial trait is more frequent in one sex than in the other, the risk is higher for relatives of patients of the less susceptible sex An affected person of the less susceptible sex is likely to have a higher liability, and thus any relative has a greater risk of being affected 7. If the concordance rate in dz twins is less than half the rate in mz twins the trait cannot be antosomal dominant and if it is less than a quarter ofthe Mz rate, it cannot be autosomal recessive The concordance rate for non-insulin-dep endent diabetes mellitus(NIDDM) is close to 100 percent in Mz twins but only about 10% in DZ pairs; at first glance the mz data support a single-gene model with complete penetrance, but the low concordance rate in DZ twins contradicts this impression, and further studies have supported the conclusion that NIDDM has complex etiology 8. An increased recurrence risk when the parents are consanguineous suggests that multiple factors with additive effects may be involved For multifactorial traits, the risk to subsequent sibs increased when the parents are consanguineous. This is in contrast to autosomal recessive inher itance; although parental consanguinity usually indicates a high probability of autosomal recessive inheritance, the recurrence risk(174)is the same whether the parents are consanguineous or not 二、遗传度及其估算
7 affected. Multiple cases suggest that the liability is high in that particular family. In contrast, for single-gene traits the risk to the next child remains unchanged even after two, three, or more affected children have been born. 5.The more severe the malformation, the greater the recurrence risk. More severely affected patients, and their relatives, have greater liability. 6.If a multifactorial trait is more frequent in one sex than in the other, the risk is higher for relatives of patients of the less susceptible sex. An affected person of the less susceptible sex is likely to have a higher liability, and thus any relative has a greater risk of being affected. 7.If the concordance rate in DZ twins is less than half the rate in MZ twins, the trait cannot be antosomal dominant, and if it is less than a quarter of the MZ rate, it cannot be autosomal recessive. The concordance rate for non-insulin-dependent diabetes mellitus(NIDDM) is close to 100 percent in MZ twins but only about 10% in DZ pairs; at first glance the MZ data support a single-gene model with complete penetrance, but the low concordance rate in DZ twins contradicts this impression, and further studies have supported the conclusion that NIDDM has complex etiology. 8.An increased recurrence risk when the parents are consanguineous suggests that multiple factors with additive effects may be involved. For multifactorial traits, the risk to subsequent sibs increased when the parents are consanguineous. This is in contrast to autosomal recessive inheritance; although parental consanguinity usually indicates a high probability of autosomal recessive inheritance, the recurrence risk (1/4) is the same whether the parents are consanguineous or not. 二、遗传度及其估算