My facination with quantitative genetics can be explained with a simple example. We know that particular variants within the Brca1 gene most certainly increase one’s chances of developing breast cancer and/or ovarian caner. To a statistical geneticist, these variants have a “large effect”, in that if you possess them, you most likely or most certainly will develop the trait/disease. However, variants such as those Angelina Jolie Pitt caries within her Brca1 gene are said to contribute very little to the genetic variance of breast cancer and ovarian cancer.
What does that mean? Well if a sample of breast cancer patients are studied, you will find that most of them do not possess the same mutations that Angelina Jolie has in her Brca1 gene. Actually, mutations like Angelina’s only account for ~2% of breast cancer patients, so you could say that the Brca1 mutation, however important, reveals only a small portion of the breast cancer mystery. Therefore, it is not just the effect size of a variant that determines the variance it contributes to a trait, but the frequency that it occurs within a population.
Whereas molecular genetics can be used to discover a handful of large effect loci, and thereby provide valuable knowledge that can contribute to the design of genetic therapies for those that have mutations at those loci, it is quantitative genetics that has potential to reveal the full picture of complex traits, albeit at the cost of understanding less of the molecular basis of the pathogenesis.