Treasure Your Marginal Genetic Effects

The prologue of the book about Bateson that I mentioned in my August 4th, 2009 post below has a great quote:

"Nevertheless, if I may throw out a word of council to beginners, it is: Treasure your exceptions! When there are none, the work gets so dull that noone cares to carry it further. Keep them always uncovered and in sight. Exceptions are like the rough brickwork of a growing building which tells that there is more to come and shows where the next construction is to be." William Bateson 1908

Bateson was likely referring to the exceptions to Mendelian principles of heredity (e.g. epistasis). We now know that the exceptions Bateson was referring to are the norm in human genetics. GWAS has very clearly shown that genetic variants with large marginal effects are indeed the exception and thus should be treasured. If it weren't for ApoE there would be a lot less excitement for the role of genetics in complex diseases.