Wang Yuanjia, Ottman Ruth, Rabinowitz Daniel
Department of Statistics, Columbia University, New York, New York 10027, USA.
Biometrics. 2006 Dec;62(4):1081-8. doi: 10.1111/j.1541-0420.2006.00614.x.
When a gene variant is discovered to segregate with a disease, it may be of interest to estimate the risk (or the age-specific risk) of the disease to carriers of the variant. The families that contributed to the discovery of the variant would typically contain multiple carriers, and so, especially if the variant is rare, might prove a valuable source of study subjects for estimation of the risk. These families, by virtue of having brought the gene in question to the attention of researchers, however, may not be representative of the relationship between carrier status and the risk of the disease in the population. Using these families for risk estimation could bias the observed association between the variant and the risk. The purpose here is to present an approach to adjusting for the potential bias while using the families from linkage analysis to estimate the risk.
当发现一个基因变异与一种疾病共分离时，估计该变异携带者患该疾病的风险（或特定年龄风险）可能会很有意义。促成该变异发现的家族通常会包含多个携带者，所以，特别是如果该变异很罕见，这些家族可能会成为估计风险的研究对象的宝贵来源。然而，正是由于这些家族使相关基因受到了研究人员的关注，它们可能并不代表人群中携带者状态与疾病风险之间的关系。使用这些家族进行风险估计可能会使观察到的变异与风险之间的关联产生偏差。本文的目的是提出一种方法，在利用连锁分析中的家族估计风险时，对潜在偏差进行校正。
