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Abstract
Letters to the Editor 457 outcome than a direct intervention because of the specific pathway affected by the variant, such as the effect of kringle IV type 2 size polymorphisms on lipoprotein (a), and the subsequent association with myocardial infarction(5). While statistical guidance on assessment of the validity of IVs in Mendelian randomization is welcome (6), there is a danger of overreliance on empirical testing at the expense of biologic knowledge (7). The statements provided by Glymour et al., while providing useful guidance, should not be seen as absolute indicators of the invalidity of an IV and should supplement rather than replace sound scientific judgment (8).
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