Liang Yannis Yan, Zhou Mingqing, He Yu, Zhang Weijie, Wu Qiqi, Luo Tong, Zhang Jun, Jia Fujun, Qi Lu, Ai Sizhi, Zhang Jihui
Center for Sleep and Circadian Medicine, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, China.
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China.
Nat Hum Behav. 2024 Nov;8(11):2209-2221. doi: 10.1038/s41562-024-01970-0. Epub 2024 Sep 16.
Loneliness-the subjective experience of social disconnection-is now widely regarded as a health risk factor. However, whether the associations between loneliness and multiple diseases are consistent with causal effects remains largely unexplored. Here we combined behavioural, genetic and hospitalization data from the UK Biobank to examine the associations of loneliness with a wide range of non-overlapping diseases. During a median 12.2-year follow-up, loneliness was associated with greater risks in 13 of 14 disease categories and 30 of 56 individual diseases considered. Of the 30 diseases significantly associated with loneliness, 26 had genetic data available for Mendelian randomization (MR) analyses. After Benjamini‒Hochberg correction and multiple sensitivity analyses within the MR framework, non-causal associations were identified between genetic liability to loneliness and 20 out of the 26 specific diseases, including cardiovascular diseases, type 2 diabetes mellitus, obesity, chronic liver diseases, chronic kidney disease, most neurological diseases and the other common diseases. Genetic liability to loneliness was only potentially causally associated with the remaining six diseases. Socioeconomic factors, health behaviours, baseline depressive symptoms and comorbidities largely explained the associations between loneliness and diseases. Overall, our study revealed a dissociation between observational and genetic evidence regarding the associations of loneliness with multiple diseases. These findings suggest that loneliness may serve as a potential surrogate marker rather than a causal risk factor for most diseases tested here.
孤独——社交隔离的主观体验——如今被广泛视为一种健康风险因素。然而，孤独与多种疾病之间的关联是否符合因果效应，在很大程度上仍未得到探究。在此，我们结合了英国生物银行的行为、基因和住院数据，以研究孤独与一系列互不重叠的疾病之间的关联。在中位时间为12.2年的随访期间，在14种疾病类别中的13种以及所考虑的56种个体疾病中的30种中，孤独与更高的风险相关。在与孤独显著相关的30种疾病中，有26种具备可用于孟德尔随机化（MR）分析的基因数据。在MR框架内进行本雅明尼-霍奇伯格校正和多次敏感性分析后，在孤独的遗传易感性与26种特定疾病中的20种之间发现了非因果关联，这些疾病包括心血管疾病、2型糖尿病、肥胖症、慢性肝病、慢性肾病、大多数神经系统疾病以及其他常见疾病。孤独的遗传易感性仅可能与其余六种疾病存在因果关联。社会经济因素、健康行为、基线抑郁症状和合并症在很大程度上解释了孤独与疾病之间的关联。总体而言，我们的研究揭示了关于孤独与多种疾病关联的观察性证据和基因证据之间的脱节。这些发现表明，对于此处所测试的大多数疾病而言，孤独可能是一种潜在的替代标志物，而非因果风险因素。
