Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Age Ageing. 2024 Jul 2;53(7). doi: 10.1093/ageing/afae163.
Visual impairment (VI) is associated with dementia and other neuropsychiatric outcomes, but previous studies have not considered genetic sources of confounding or effect modification.
We analysed data from the Health and Retirement Study, an ongoing nationally representative survey of older US adults, a subset of whom underwent genetic testing from 2006 to 2012 (n = 13 465). Using discrete time proportional hazards models and generalised estimating equations, we measured the association between VI and dementia, depression and hallucinations adjusting for demographics and comorbidities, ancestry-specific principal components and polygenic risk scores (PRS) for Alzheimer's disease, major depressive disorder or schizophrenia. Effect modification was assessed using VI-PRS interaction terms and stratified analyses.
VI was associated with dementia, depression and hallucinations after adjusting polygenic risk and other confounders. There was no VI-PRS interaction for dementia or depression. However, the association between VI and hallucinations varied by genetic risk of schizophrenia. Within the bottom four quintiles of schizophrenia PRS, VI was not associated with hallucinations among White (OR 1.16, 95% CI: 0.87-1.55) or Black participants (OR 0.96, 95% CI: 0.49-1.89). In contrast, VI was strongly associated with hallucinations among White (OR 2.08, 95% CI: 1.17-3.71) and Black (OR 10.63, 95% CI: 1.74-65.03) participants in the top quintile of schizophrenia PRS.
The association between VI and neuropsychiatric outcomes is not explained by shared genetic risk factors, and there is a significant interaction between VI and polygenic risk of hallucinations in older adults.
视力障碍（VI）与痴呆症和其他神经精神结局相关，但先前的研究并未考虑混杂因素或效应修饰的遗传来源。
我们分析了来自健康与退休研究的数据，这是一项针对美国老年人的全国代表性调查，其中一部分人在 2006 年至 2012 年期间接受了基因检测（n=13465）。我们使用离散时间比例风险模型和广义估计方程，在调整人口统计学和合并症、特定祖先的主成分和阿尔茨海默病、重度抑郁症或精神分裂症的多基因风险评分（PRS）后，测量了 VI 与痴呆症、抑郁症和幻觉之间的关联。使用 VI-PRS 交互项和分层分析评估了效应修饰。
VI 与调整后的多基因风险和其他混杂因素后的痴呆症、抑郁症和幻觉相关。痴呆症或抑郁症没有 VI-PRS 交互作用。然而，VI 与幻觉之间的关联因精神分裂症的遗传风险而异。在精神分裂症 PRS 的最低四分之一中，VI 与白人（OR 1.16，95%CI：0.87-1.55）或黑人参与者（OR 0.96，95%CI：0.49-1.89）的幻觉无关。相比之下，VI 与精神分裂症 PRS 最高五分位数的白人（OR 2.08，95%CI：1.17-3.71）和黑人（OR 10.63，95%CI：1.74-65.03）参与者的幻觉强烈相关。
VI 与神经精神结局之间的关联不能用共同的遗传风险因素来解释，而且在老年人中 VI 与幻觉的多基因风险之间存在显著的相互作用。
