Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort
Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort
复制标题
DOI：
10.1038/s41380-019-0395-3
复制
发表时间：
2020-07-01
影响因子：
11
通讯作者：
Burgess, Stephen
中科院分区：
文献类型：
--
作者：
Khandaker, Golam M.;Zuber, Verena;Burgess, Stephen
虽然冠心病（CHD）和抑郁症之间的共病是显而易见的，但尚不清楚这两种疾病是否有共同的潜在机制。我们对来自英国生物银行（一项基于人群的队列研究）的367，703名欧洲血统的无关中年参与者进行了一系列分析，以评估合并症是否主要是由于遗传或环境因素，并使用孟德尔随机化方法测试心血管危险因素和CHD是否可能与抑郁症有因果关系。我们发现心脏病家族史与抑郁风险增加20%相关（95%可信区间[CI] 16- 24%，p < 0.0001），但与CHD风险密切相关的遗传风险评分与抑郁无关。CHD遗传风险评分增加1个标准差与CHD风险增加71%相关，但抑郁风险增加1%（95%CI 0-3%;p = 0.11）。孟德尔随机化分析表明，甘油三酯，白细胞介素-6（IL-6）和C-反应蛋白（CRP）可能是抑郁症的因果危险因素。遗传学预测的甘油三酯每增加一个标准差，抑郁症的比值比为1.18（95% CI 1.09-1.27;p = 2 x 10（-5））;遗传预测对数转换的IL-6每单位增加0.74（95% CI 0.62-0.89;p = 0.0012）;遗传预测对数转换CRP每单位增加为1.18（95% CI 1.07-1.29;p = 0.0009）。我们的分析表明，抑郁症和冠心病之间的共病主要来自共同的环境因素。IL-6、CRP和甘油三酯可能与抑郁症有因果关系，因此可能成为治疗和预防抑郁症的靶点。
While comorbidity between coronary heart disease (CHD) and depression is evident, it is unclear whether the two diseases have shared underlying mechanisms. We performed a range of analyses in 367,703 unrelated middle-aged participants of European ancestry from UK Biobank, a population-based cohort study, to assess whether comorbidity is primarily due to genetic or environmental factors, and to test whether cardiovascular risk factors and CHD are likely to be causally related to depression using Mendelian randomization. We showed family history of heart disease was associated with a 20% increase in depression risk (95% confidence interval [CI] 16-24%,p < 0.0001), but a genetic risk score that is strongly associated with CHD risk was not associated with depression. An increase of 1 standard deviation in the CHD genetic risk score was associated with 71% higher CHD risk, but 1% higher depression risk (95% CI 0-3%;p = 0.11). Mendelian randomization analyses suggested that triglycerides, interleukin-6 (IL-6), and C-reactive protein (CRP) are likely causal risk factors for depression. The odds ratio for depression per standard deviation increase in genetically-predicted triglycerides was 1.18 (95% CI 1.09-1.27;p = 2 x 10(-5)); per unit increase in genetically-predicted log-transformed IL-6 was 0.74 (95% CI 0.62-0.89;p = 0.0012); and per unit increase in genetically-predicted log-transformed CRP was 1.18 (95% CI 1.07-1.29;p = 0.0009). Our analyses suggest that comorbidity between depression and CHD arises largely from shared environmental factors. IL-6, CRP and triglycerides are likely to be causally linked with depression, so could be targets for treatment and prevention of depression.