Wilcox A J, Weinberg C R, Lie R T
Epidemiology Branch, NIEHS, Research Triangle Park, NC 27709, USA.
Am J Epidemiol. 1998 Nov 1;148(9):893-901. doi: 10.1093/oxfordjournals.aje.a009715.
A gene variant that increases disease risk will be overrepresented among diseased persons, even compared with their own biologic parents. This insight has led to tests based solely on the asymmetric distribution of a variant allele among cases and their parents (e.g., the transmission/disequilibrium test). Existing methods focus on effects of alleles that operate through the offspring genotype. Alleles can also operate through the mother's genotype, particularly for conditions such as birth defects that have their origins in fetal life. An allele working through the mother would have higher frequency in case-mothers than in case-fathers. The authors develop a log-linear method for estimating relative risks for alleles in the context of case-parent triads. This method is able to detect the effects of genes working through the offspring, the mother, or both. The authors assume Mendelian inheritance, but Hardy-Weinberg equilibrium is unnecessary. Their approach uses standard software, and simulations demonstrate satisfactory power and confidence interval coverage. This method is valid with a self-selected or hospital-based series of cases and helps to protect against misleading inference that can result when cases and controls are randomly sampled from a population not in Hardy-Weinberg equilibrium.
一种增加疾病风险的基因变异在患病个体中会过度出现，即使与他们自己的生物学父母相比也是如此。这一见解催生了仅基于变异等位基因在病例及其父母中的不对称分布的检测方法（例如，传递/不平衡检测）。现有方法关注通过后代基因型起作用的等位基因的效应。等位基因也可以通过母亲的基因型起作用，特别是对于诸如出生缺陷这类起源于胎儿期的病症。通过母亲起作用的等位基因在病例母亲中出现的频率会高于病例父亲。作者们开发了一种对数线性方法，用于在病例 - 父母三联体的背景下估计等位基因的相对风险。这种方法能够检测通过后代、母亲或两者起作用的基因的效应。作者们假设孟德尔遗传，但哈迪 - 温伯格平衡并非必要条件。他们的方法使用标准软件，模拟结果显示出令人满意的功效和置信区间覆盖范围。这种方法对于自行选择的或基于医院的病例系列是有效的，并且有助于防止在从非哈迪 - 温伯格平衡的人群中随机抽取病例和对照时可能产生的误导性推断。
