Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Clin Gastroenterol Hepatol. 2023 Feb;21(2):398-405.e4. doi: 10.1016/j.cgh.2022.01.021. Epub 2022 Jan 31.
BACKGROUND & AIMS: Serum 25-hydroxyvitamin D [S-25(OH)D] and nonalcoholic fatty liver disease (NAFLD) are correlated in many observational studies, whereas the causality of this association is uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to determine the association between S-25(OH)D and NAFLD.
Seven and 6 independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide-significance level, respectively, were selected as instrumental variables. Summary-level data for S-25(OH)D were obtained from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium including 79,366 individuals. Summary-level data for NAFLD were available from a genome-wide association meta-analysis (1483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls), and the UK Biobank study (275 cases and 360,919 controls). Summary-level data for 4 liver enzymes were obtained from the UK Biobank.
There were genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes. Genetically predicted higher levels of S-25(OH)D were consistently associated with a decreased risk of NAFLD in the 3 sources. For a 1-SD increase in genetically predicted S-25(OH)D levels, the combined odds ratio of NAFLD was 0.78 (95% confidence interval [CI], 0.69 to 0.89). Genetically predicted higher levels of S-25(OH)D showed a borderline association with aspartate aminotransferase levels (change -1.17; 95% CI, -1.36 to 0.01). Genetic predisposition to NAFLD was not associated with S-25(OH)D (change 0.13; 95% CI, -1.26 to 0.53).
Our findings have clinical implications as they suggest that increased vitamin D levels may play a role in NAFLD prevention in European populations.
在许多观察性研究中，血清 25-羟维生素 D [S-25(OH)D] 与非酒精性脂肪性肝病 (NAFLD) 相关，而这种关联的因果关系尚不确定，尤其是在欧洲人群中。我们进行了一项双向 Mendelian 随机化研究，以确定 S-25(OH)D 与 NAFLD 之间的关联。
分别选择与 S-25(OH)D 和 NAFLD 具有全基因组显著性水平相关的 7 个和 6 个独立遗传变异作为工具变量。S-25(OH)D 的汇总水平数据来自于包括 79366 个人的研究基础遗传决定因素的维生素 D 和高度相关特征联盟。NAFLD 的汇总水平数据可从全基因组关联荟萃分析（1483 例病例和 17781 例对照）、芬兰人联盟（894 例病例和 217898 例对照）和英国生物库研究（275 例病例和 360919 例对照）中获得。4 种肝酶的汇总水平数据来自英国生物库。
S-25(OH)D 与 NAFLD 和某些肝酶之间存在遗传相关性。在 3 个来源中，遗传预测的 S-25(OH)D 水平升高与 NAFLD 的风险降低一致相关。对于遗传预测的 S-25(OH)D 水平升高 1-SD，NAFLD 的合并优势比为 0.78（95%置信区间[CI]，0.69 至 0.89）。遗传预测的 S-25(OH)D 水平升高与天门冬氨酸氨基转移酶水平呈边缘关联（变化-1.17；95%CI，-1.36 至 0.01）。NAFLD 的遗传易感性与 S-25(OH)D 无关（变化 0.13；95%CI，-1.26 至 0.53）。
我们的研究结果具有临床意义，因为它们表明维生素 D 水平升高可能在欧洲人群中发挥预防 NAFLD 的作用。
