A technical argument against all common variant models is that association alone is insufficient evidence of function: correlation is not causation. Very few of the thousands of GWAS significant associations have been shown using molecular genetics, biochemistry or biophysics to be the actual risk variant38, 109. In this context, prudence suggests an open mind in each individual case as to whether the variant, another common variant in LD, or a series of less common variants of large effect synthetically associated may be responsible. The case of protection against anemia in chronic hepatitis C, where the initial GWAS discovery clearly captures two less common causal coding variants at the ITPA locus, is a good example110.
