Conditioning for CAD, AF and blood pressure traits demonstrated that the effects of some loci (e.g., 9p21/CDKN2B-AS1) were mediated wholly via risk factor trait associations (e.g., CAD); however, for 8 of 12 variants the attenuation of effects was <50%, suggesting alternative mechanisms may be important. This evidence concerns the gene CDKN2B and atrial fibrillation.