Estimation and partitioning of the still-missing heritability for complex disease

我们率先在人类遗传学中使用多标记统计遗传方法来阐明复杂性状的遗传结构，包括常见疾病。我们已经证明，三分之一到一半的可加性遗传变异被普通遗传变异捕获，剩下三分之二到一半真正“缺失”。在本提案中，我们将检验我们的假设，即仍然缺失的遗传性是由于低频因果变异。基因组医学的应用需要这些基础知识的充分发展。

We have pioneered the use of multi-marker statistical genetic methods in human genetics to elucidate the genetic architecture of complex traits, including common diseases. We have shown that between a third and a half of additive genetic variation is captured by common genetic variants, leaving two-thirds to a half truly ‘missing’. In this proposal we will test our hypothesis that the still-missing heritability is due to low frequency causal variants. Applications of genomic medicine require this fundamental knowledge to progress fully.