Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases: A Mendelian Randomization Study.
Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases: A Mendelian Randomization Study.
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DOI：
10.2215/cjn.05080422
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发表时间：
2023-01-01
期刊：
影响因子：
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通讯作者：
on behalf of the SCALLOP Consortium
中科院分区：
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作者：
Donovan K;Herrington WG;Paré G;Pigeyre M;Haynes R;Sardell R;Butterworth AS;Folkersen L;Gustafsson S;Wang Q;Baigent C;Mälarstig A;Holmes MV;Staplin N;on behalf of the SCALLOP Consortium
成纤维细胞生长因子-23（FGF-23）在传统流行病学研究中与一系列心血管和非心血管疾病相关，但可能存在大量残留混杂因素。孟德尔随机化方法可以帮助控制这种混淆。SCALLOP Consortium的19，195名参与者的数据被用于生成FGF-23遗传评分。来自337，448名英国生物银行参与者的数据用于估计遗传预测的FGF-23浓度较高与任何动脉粥样硬化性心血管疾病（n= 26，266事件），非动脉粥样硬化性心血管疾病（n= 12，652）和先前与FGF-23相关的非心血管疾病之间的关联。颈动脉内膜中层厚度和左心室质量的测量结果在一个子集中可用。还在三个大型病例对照联合体中检验了与心血管结局的相关性：CARDIOGRAMplusC 4 D（冠状动脉疾病，n= 181，249例）、MEGASTROKE（卒中，n= 34，217）和爱马仕（心力衰竭，n= 47，309）。我们确定了循环FGF-23的34个独立变体，形成了一个有效的遗传评分。遗传预测的FGF-23与任何心血管或非心血管结局之间均无相关性。在英国生物样本库中，任何动脉粥样硬化性心血管疾病每1-SD高遗传预测logFGF-23的比值比（OR）为1.03（95%置信区间[95% CI]，0.98 - 1.08），任何非动脉粥样硬化性心血管疾病的比值比为1.01（95% CI，0.94 - 1.09）。病例对照联合体中冠状动脉疾病的OR为1.00（95% CI，0.97 - 1.03），卒中为1.01（95% CI，0.95 - 1.07），心力衰竭为1.00（95% CI，0.95 - 1.05）。在那些有影像学检查的患者中，logFGF-23与颈动脉或心脏异常无关。遗传学预测的FGF-23水平与动脉粥样硬化和非动脉粥样硬化性心血管疾病无关，表明没有重要的因果关系。本文包含播客https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_01_10_CJN05080422.mp3
Fibroblast growth factor-23 (FGF-23) is associated with a range of cardiovascular and noncardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding. SCALLOP Consortium data of 19,195 participants were used to generate an FGF-23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), nonatherosclerotic cardiovascular disease (n=12,652), and noncardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309). We identified 34 independent variants for circulating FGF-23, which formed a validated genetic score. There were no associations between genetically predicted FGF-23 and any of the cardiovascular or noncardiovascular outcomes. In UK Biobank, the odds ratio (OR) for any atherosclerotic cardiovascular disease per 1-SD higher genetically predicted logFGF-23 was 1.03 (95% confidence interval [95% CI], 0.98 to 1.08), and for any nonatherosclerotic cardiovascular disease, it was 1.01 (95% CI, 0.94 to 1.09). The ORs in the case-control consortia were 1.00 (95% CI, 0.97 to 1.03) for coronary artery disease, 1.01 (95% CI, 0.95 to 1.07) for stroke, and 1.00 (95% CI, 0.95 to 1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalities. Genetically predicted FGF-23 levels are not associated with atherosclerotic and nonatherosclerotic cardiovascular diseases, suggesting no important causal link. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_01_10_CJN05080422.mp3