ENPP1 and diabetes mellitus: This discrepancy might be inherent to differences between hypothesis-driven and hypothesis-free approaches: the hypothesis-free GWA studies provided a series of novel diabetes risk genes with modest effect sizes and largely unknown biological functions, whereas some very strong biological candidate genes with meta-analysis-proven effects on type 2 diabetes risk, such as CAPN10 and ENPP1, have not been replicated by GWA studies.