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Correspondence

Mendelian Randomization Study of ACLY and Cardiovascular Disease

To the Editor: Ference et al. (March 14, 2019, issue)1 tested the association of plasma low-density lipoprotein (LDL) cholesterol and cardiovascular disease with genetic variants in a 1-million-base span around the gene encoding ATP citrate lyase (ACLY) and concluded that human genetics validates ACLY as a therapeutic target for cardiovascular disease. Compelling support for this assertion requires that the utilized genetic variants capture inborn variability in the activity of ACLY.2 However, none of the variants were shown by Ference et al. to affect the quantity or quality of the ACLY gene product. Support for the authors’ assertion also requires that . . .

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