The associations of alcoholic liver disease and nonalcoholic fatty liver disease with bone mineral density and the mediation of serum 25-Hydroxyvitamin D: A bidirectional and two-step Mendelian randomization.

Genetically determined serum 25-OHD levels were associated with an increasing trend in FN-BMD (beta = 0.126; 95%CI: 0.0512,0.201; P = 0.000976) (S21 Table of S1 File ), but not in TB-BMD, LS-BMD, or FA-BMD (S21 Table of S1 File ).

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Estimating the effect of ALD, NAFLD, and potential mediators on BMD As shown in Fig 2 , genetically determined ALD was significantly associated with a decreasing trend of FN-BMD at the Bonferroni corrected significance of P < 0.0125 (IVW beta = -0.0288; 95% CI: -0.0488, -0.00871; P = 0.00494).

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The results of the MR-Egger (beta = -0.00822; 95% CI: -0.0464, 0.0300; P = 0.682), weighted median (beta = -0.0200; 95% CI: -0.0473, 0.00732; P = 0.151), weighted mode (beta = -0.0155; 95% CI: -0.0485, 0.0175; P = 0.377) and MR-RAPS (beta = -0.0282; 95%CI: -0.0508, 0.00563; P = 0.0143) yielded similar trends, although the P values did not reach statistical significance ( Fig 2 ).

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