The article entitled ‘A remark on rare variants’ by Oexle1 is an interesting report in which the author describes an approach to the study of common diseases caused by multiple rare variants. The article contains three parts. The first part is a discussion of the concept of population attributable risk (PAR) proposed by Bodmer and Bonilla.2 PAR is a kind of index that represents the contribution of a variant to the onset of the disease. For calculating the cumulative genetic effect of rare variants, an approximate expression for estimating PAR is presented. However, the explanation of PAR in the original article is difficult to understand because it does not go into enough detail. The author explained the process of obtaining the equations described in the original article. The second part is a discussion of the efficiency of genetic analysis for rare variants with strong effect size. The powers of both affected sib-pair analysis and transmission/disequilibrium test (TDT) were calculated based on the methods of Risch and Merikangas.3 The author illustrated that affected sib-pair analysis is more sensitive to a decrease in frequency or effect size than TDT. The third part proposes a disease model based on Kimura's infinite sites model. The author derived a simple relationship between the variant's selection coefficient and its effect size. The number of contributing genetic variants can be estimated by this model. Finally, TDT was applied to the disease model. The author derived the required sample size for the test.

The first two parts are very informative and contribute to the understanding of original articles. Moreover, I find the disease model proposed in the third part very intriguing.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD