Question

A genome-wide association study can identify new variants associated with a condition, and the data can be used to calculate an odds ratio, which is the ratio of the odds of having a condition if an individual has a variant. For example, a variant with an odds ratio of 3 means that individuals with that variant are three times more likely to have the condition than those who do not. Which of the following statements is NOT true?

A variant that lowers risk of developing a condition will have an odds ratio less than one.

A variant that is not associated with a condition will have an odds ratio of one.

A Mendelian variant will have a higher odds ratio than a complex variant.

The penetrance of a variant will not affect the odds ratio.

Answer 1

The odds ratio is the value eb where b is the estimated increase in the log odds of outcome (eg developing a specific condition) with an increase in the exposure (i.e if one has the gene variant)

So, an odds ratio of 1 means b is zero, so there is no effect of that particular variant on the condition.

  an odds ratio of less than 1 means b is negative, so that particular variant reduces the risk of developing the condition

an odds ratio of more than 1 means b is positive, so that particular variant increases the risk of developing the condition.

Penetrance is the likelihood of showing a phenotype if the gene is present and it definitely affects the odds ratio since a lower penetrance means that the odds of developing the condition are lower and vice versa.

However, the odds ratio of a complex trait is additive and depends on multiple factors whereas, for Mendelian inheritance, it only depend on the alleles of the gene present. So, Mendelian variant normally have lesser odds ratio as compared to complex variants.