Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Eur J Neurol. 2022 Jul;29(7):2066-2073. doi: 10.1111/ene.15311. Epub 2022 Mar 18.
Chronic axonal polyneuropathy is a common disease, but the etiology remains only partially understood. Previous etiologic studies have identified clinical risk factors, but genetic evidence supporting causality between these factors and polyneuropathy are largely lacking. In this study, we investigate whether there is a genetic association of clinically established important risk factors (diabetes, body mass index [BMI], vitamin B12 levels, and alcohol intake) with chronic axonal polyneuropathy.
This study was performed within the population-based Rotterdam Study and included 1565 participants (median age = 73.6 years, interquartile range = 64.6-78.8, 53.5% female), of whom 215 participants (13.7%) had polyneuropathy. Polygenic scores (PGSs) for diabetes, BMI, vitamin B12 levels, and alcohol intake were calculated at multiple significance thresholds based on published genome-wide association studies.
Higher PGSs of diabetes, BMI, and alcohol intake were associated with higher prevalence of chronic axonal polyneuropathy, whereas higher PGS of vitamin B12 levels was associated with lower prevalence of polyneuropathy. These effects were most pronounced for PGSs with lenient significance thresholds for diabetes and BMI (odds ratio [OR] = 1.21, 95% confidence interval [CI] = 1.05-1.39 and OR = 1.21, 95% CI = 1.04-1.41) and for the strictest significance thresholds for vitamin B12 level and alcohol intake (OR = 0.79, 95% CI = 0.68-0.92 and OR = 1.17, 95% CI = 1.02-1.35). We did not find an association between different PGSs and sural sensory nerve action potential amplitude, nor between individual lead variants of PGS and polyneuropathy.
This study provides evidence for polygenic associations of diabetes, BMI, vitamin B12 level, and alcohol intake with chronic axonal polyneuropathy. This supports the hypothesis of causal associations between well-known clinical risk factors and polyneuropathy.
慢性轴索性多发性神经病是一种常见疾病，但病因仍不完全清楚。先前的病因研究已经确定了临床危险因素，但缺乏这些因素与多发性神经病之间因果关系的遗传证据。在这项研究中，我们调查了临床上确定的重要危险因素（糖尿病、体重指数[BMI]、维生素 B12 水平和酒精摄入）与慢性轴索性多发性神经病之间是否存在遗传关联。
本研究在基于人群的鹿特丹研究中进行，纳入了 1565 名参与者（中位年龄=73.6 岁，四分位间距=64.6-78.8，53.5%为女性），其中 215 名（13.7%）患有多发性神经病。根据已发表的全基因组关联研究，在多个显著阈值下计算了糖尿病、BMI、维生素 B12 水平和酒精摄入的多基因评分（PGS）。
较高的糖尿病、BMI 和酒精摄入 PGS 与慢性轴索性多发性神经病的患病率较高相关，而较高的维生素 B12 水平 PGS 与多发性神经病的患病率较低相关。这些影响在糖尿病和 BMI 的宽松显著性阈值的 PGS 中最为明显（比值比[OR] 1.21，95%置信区间[CI] 1.05-1.39 和 OR 1.21，95% CI 1.04-1.41），而在维生素 B12 水平和酒精摄入的最严格显著性阈值的 PGS 中最为明显（OR 0.79，95% CI 0.68-0.92 和 OR 1.17，95% CI 1.02-1.35）。我们没有发现不同的 PGS 与腓肠神经感觉神经动作电位幅度之间存在关联，也没有发现 PGS 的个体先导变异与多发性神经病之间存在关联。
本研究为糖尿病、BMI、维生素 B12 水平和酒精摄入与慢性轴索性多发性神经病之间的多基因关联提供了证据。这支持了已知临床危险因素与多发性神经病之间存在因果关系的假说。
