Population screening for carrier status: effects of test limitations on precision of carrier prevalence rates.
Population screening for carrier status: effects of test limitations on precision of carrier prevalence rates.
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携带者状态的人群筛查：测试限制对携带者患病率精度的影响。
DOI：
10.1002/ajmg.1320490315
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Phillips3rd,JA
中科院分区：
文献类型：
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作者：
Parker,RA;Phillips3rd,JA
由于遗传异质性和模糊性的测试结果，只有很少会携带者筛选确定所有携带者的一个给定的常染色体隐性遗传病。然而，通过测试识别的载波的分数可以在案例频率研究中估计。然后，群体携带率是在群体筛查研究中观察到的比率除以在病例频率研究中估计的通过筛查测试检测到的所有缺陷等位基因的分数。例如，假设在群体筛选期间发现3%的群体携带囊性纤维化（CF）的AF 508突变。如果在同一人群中进行的病例频率研究发现CF病例的75%的等位基因代表ΔF508突变，则估计的人群携带率为4%（= 0.03/0.75）。该估计的精确度涉及病例频率研究中检测到的携带者比例和人群筛查研究中观察到的携带者比例的精确度。用于估计置信区间和样本量的标准公式仅考虑群体筛选研究中的变异性。由于这些公式低估了群体携带率估计值的真实变异性，因此为群体筛查研究计算的样本量也被低估。我们提出的公式，将这两个因素的变异性，并说明了这种额外的变异性的估计和样本量的置信限的影响时，规划一项研究。© 1994 Wiley利斯公司
Because of genetic heterogeneity and ambiguity of test results, only rarely will carrier screening identify all carriers of a given autosomal recessive disorder. However, the fraction of carriers identified by the test can be estimated in a case frequency study. The population carrier rate then is the rate observed in a population screening study divided by the fraction of all defective alleles detected by the screening test, estimated in the case frequency study. For example, suppose 3% of a population are found to carry the AF508 mutation for cystic fibrosis (CF) during population screening. If a case frequency study in this same population finds that 75% of the alleles of CF cases represent the ΔF508 mutation, then the estimated population carrier rate is 4% (= .03/.75). The precision of this estimate involves the precision of both the fraction of carriers detected in the case frequency study and the proportion of carriers observed in the population screening study. Standard formulae for estimating the confidence interval and sample size consider only the variability in the population screening study. Since these formulae underestimate the true variability of the estimate of the population carrier rate, the sample size calculated for a population screening study is also underestimated. We present formulae which incorporate the variability in both factors, and illustrate the effect of this additional variability on confidence limits for estimtes and sample size when planning a study. © 1994 Wiley‐Liss, Inc.