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 . . .