Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, United Kingdom.
Medical Research Council Population Health Research Unit at the University of Oxford, NDPH, Oxford, United Kingdom.
Clin J Am Soc Nephrol. 2023 Jan 1;18(1):17-27. doi: 10.2215/CJN.05080422.
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.
成纤维细胞生长因子 23（FGF-23）在常规流行病学研究中与一系列心血管和非心血管疾病相关，但可能存在大量残余混杂。孟德尔随机化方法可以帮助控制这种混杂。
使用 SCALLOP 联盟的 19195 名参与者的数据生成 FGF-23 遗传评分。使用来自 337448 名英国生物库参与者的数据，估计更高的遗传预测 FGF-23 浓度与任何动脉粥样硬化性心血管疾病（n=26266 例事件）、非动脉粥样硬化性心血管疾病（n=12652）和先前与 FGF-23 相关的非心血管疾病之间的几率。在一个亚组中可测量颈动脉内膜中层厚度和左心室质量。还在三个大型病例对照联盟中测试了与心血管结局的关联：CARDIOGRAMplusC4D（冠心病，n=181249 例）、MEGASTROKE（中风，n=34217）和 HERMES（心力衰竭，n=47309）。
我们确定了 34 个用于循环 FGF-23 的独立变体，这些变体构成了一个经过验证的遗传评分。遗传预测的 FGF-23 与任何心血管或非心血管结局之间没有关联。在英国生物库中，每增加一个标准差的遗传预测 logFGF-23，任何动脉粥样硬化性心血管疾病的优势比（OR）为 1.03（95%置信区间[95%CI]，0.98 至 1.08），任何非动脉粥样硬化性心血管疾病的 OR 为 1.01（95%CI，0.94 至 1.09）。病例对照联盟中的 OR 为冠心病 1.00（95%CI，0.97 至 1.03）、中风 1.01（95%CI，0.95 至 1.07）和心力衰竭 1.00（95%CI，0.95 至 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，提示没有重要的因果关系。
本文包含一个播客，可在 https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_01_10_CJN05080422.mp3 上收听。
