Genome-wide association studies may be misinterpreted: genes versus heritability.
Genome-wide association studies may be misinterpreted: genes versus heritability.
复制标题
全基因组关联研究可能会被误解：基因与遗传力。
作者：
P. Vineis;N. Pearce
关于全基因组关联研究（GWAS）的许多文献都是基于这样一个前提，即很大一部分常见疾病是可遗传的，而这一比例很可能是由于通过广泛的DNA扫描可检测到的遗传变异。遗传率是根据家庭研究（包括双胞胎研究）估计的，并且是基于对特定家庭不同成员之间疾病变异的比较。由于GWAS结果（对常见疾病通常<10%）和遗传力估计（通常小于50%）所解释的疾病群体差异之间存在很大差距，因此产生了如何解释这些差异的问题。然而，这个问题的前提是基于两个误解来源：(i)混淆变异和因果关系，（ii）混淆遗传性和遗传决定。正如我们用许多例子所表明的那样，变异不是因果关系，遗传性也不是基因决定。因此，遗传力研究不能提供可归因于遗传因素的疾病病例比例的有效估计。这种估计又不能用来估计由环境因素引起的病例的比例。
Much of the literature on genome-wide association studies (GWAS) is based on the premise that an important proportion of common diseases is heritable and that this proportion is likely to be due to genetic variants detectable with extensive scans of the DNA. Heritability is estimated from family studies, including twin studies and is based on the comparison of the variation in disease among different members of particular families. Since there is a wide gap between the population variation in disease explained by the results of GWAS (usually <10% for common diseases) and estimates of heritability (often >50%), the question arises as to how to explain these differences. However, the premise for this question is based on two sources of misunderstanding: (i) confusion between variation and causation and (ii) confusion between heritability and genetic determination. As we show with a number of examples, variation is not causation and heritability is not genetic determination. Therefore, heritability studies do not provide valid estimates of the proportion of disease cases that are attributable to genetic factors. Such estimates in turn cannot be used to estimate the proportion of cases that are due to environmental factors.