Institute of Health Informatics, University College London, London, United Kingdom.
Health Data Research UK London, University College London, London, United Kingdom.
JAMA Ophthalmol. 2021 Dec 1;139(12):1299-1306. doi: 10.1001/jamaophthalmol.2021.4601.
Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD.
To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD.
DESIGN, SETTING, PARTICIPANTS: This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies. Summary-level statistics for these instruments were obtained for advanced AMD from the International AMD Genomics Consortium 2016 data set, which consisted of 16 144 individuals with AMD and 17 832 control individuals. Data were analyzed from July 2020 to September 2021.
Smoking initiation, smoking cessation, lifetime smoking, age at smoking initiation, alcoholic drinks per week, body mass index, systolic and diastolic blood pressure, type 2 diabetes, glycated hemoglobin, fasting glucose, and fasting insulin.
Advanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD.
A 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (odds ratio [OR], 1.26; 95% CI, 1.13-1.40; P < .001), while a 1-SD increase in logodds of genetically predicted smoking cessation (former vs current smoking) was associated with lower risk of advanced AMD (OR, 0.66; 95% CI, 0.50-0.87; P = .003). Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior, 1.32; 95% CI, 1.09-1.59; P = .004). Genetically predicted alcohol consumption was associated with higher risk of GA (OR per 1-SD increase of log-transformed alcoholic drinks per week, 2.70; 95% CI, 1.48-4.94; P = .001). There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD.
This study provides genetic evidence that increased alcohol intake may be a causal risk factor for GA. As there are currently no known treatments for GA, this finding has important public health implications. These results also support previous observational studies associating smoking behavior with risk of advanced AMD, thus reinforcing existing public health messages regarding the risk of blindness associated with smoking.
年龄相关性黄斑变性（AMD）是西方国家致盲的主要原因。需要确定与晚期 AMD 相关的因果可改变风险因素，以制定预防措施。
评估吸烟、饮酒、血压、体重指数和血糖特征是否与晚期 AMD 风险增加相关。
设计、地点、参与者：本研究使用了双样本 Mendelian 随机化。通过对全基因组关联研究（全基因组关联研究）中的风险因素进行全基因组意义上的关联分析（P < 5 × 10-8），获得了由与风险因素相关的变异组成的遗传工具。使用 2016 年国际 AMD 基因组学联盟的数据，从全基因组关联研究中获得了这些工具的高级 AMD 汇总统计数据，该数据包括 16144 名 AMD 患者和 17832 名对照个体。数据分析于 2020 年 7 月至 2021 年 9 月进行。
吸烟开始、戒烟、终生吸烟、开始吸烟年龄、每周饮酒量、体重指数、收缩压和舒张压、2 型糖尿病、糖化血红蛋白、空腹血糖和空腹胰岛素。
晚期 AMD 及其亚型，地理萎缩（GA）和新生血管性 AMD。
遗传预测的吸烟起始对数优势增加 1 个标准差与晚期 AMD 的风险增加相关（优势比[OR]，1.26；95%置信区间，1.13-1.40；P < 0.001），而遗传预测的吸烟停止（以前与现在吸烟）对数优势增加 1 个标准差与晚期 AMD 的风险降低相关（OR，0.66；95%置信区间，0.50-0.87；P = 0.003）。遗传预测的终生吸烟增加与晚期 AMD 的风险增加相关（每增加 1 个标准差的终生吸烟行为，OR 为 1.32；95%置信区间，1.09-1.59；P = 0.004）。遗传预测的饮酒与 GA 的风险增加相关（每增加 1 个标准差的每周对数转化饮酒量，OR 为 2.70；95%置信区间，1.48-4.94；P = 0.001）。没有足够的证据表明遗传预测的血压、体重指数和血糖特征与晚期 AMD 相关。
本研究提供了遗传证据，表明饮酒量增加可能是 GA 的一个因果风险因素。由于目前尚无针对 GA 的已知治疗方法，因此这一发现具有重要的公共卫生意义。这些结果还支持了先前观察性研究将吸烟行为与晚期 AMD 风险相关联的研究，从而强化了与吸烟相关的失明风险的现有公共卫生信息。
