Comments on revised manuscript

I have read authors' response and I'm mostly satisfied. Only two minor comments: * Witte 2014 Nature Rev. Genet. article summarizes the point I tried to make well. I understand that rare variants should have a relatively higher effect from an evolutionary perspective, but since these are rare, their individual or even collective contribution to a disease in the population is still small. A casual reader may not realize this point and I think it would be helpful to cite Witte's article. * My minor comment on Fig.1 is still not addressed: there seem to be more points on the right side of p=0.01 line than the left side. Why this discontinuity? (the added text in Revision is about the color and size of the dots, not about this discontinuity)