Karlsson I K, Ploner A, Song C, Gatz M, Pedersen N L, Hägg S
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Psychology, University of Southern California, Los Angeles, CA, USA.
Transl Psychiatry. 2017 May 30;7(5):e1142. doi: 10.1038/tp.2017.110.
Several studies have shown cardiovascular disease (CVD) to be associated with dementia, but it is not clear whether CVD per se increases the risk of dementia or whether the association is due to shared risk factors. We tested how a genetic risk score (GRS) for coronary artery disease (CAD) affects dementia risk after CVD in 13 231 Swedish twins. We also utilized summarized genome-wide association data to study genetic overlap between CAD and Alzheimer´s disease (AD), and additionally between shared risk factors and each disease. There was no direct effect of a CAD GRS on dementia (hazard ratio 0.99, 95% confidence interval (CI): 0.98-1.01). However, the GRS for CAD modified the association between CVD and dementia within 3 years of CVD diagnosis, ranging from a hazard ratio of 1.59 (95% CI: 1.05-2.41) in the first GRS quartile to 1.91 (95% CI: 1.28-2.86) in the fourth GRS quartile. Using summary statistics, we found no genetic overlap between CAD and AD. We did, however, find that both AD and CAD share a significant genetic overlap with lipids, but that the overlap arose from clearly distinct gene clusters. In conclusion, genetic susceptibility to CAD was found to modify the association between CVD and dementia, most likely through associations with shared risk factors.
多项研究表明心血管疾病（CVD）与痴呆症有关，但尚不清楚CVD本身是否会增加痴呆症风险，或者这种关联是否归因于共同的风险因素。我们在13231名瑞典双胞胎中测试了冠心病（CAD）的遗传风险评分（GRS）如何影响CVD后的痴呆症风险。我们还利用汇总的全基因组关联数据来研究CAD与阿尔茨海默病（AD）之间的遗传重叠，以及共同风险因素与每种疾病之间的遗传重叠。CAD的GRS对痴呆症没有直接影响（风险比0.99，95%置信区间（CI）：0.98 - 1.01）。然而，CAD的GRS在CVD诊断后的3年内改变了CVD与痴呆症之间的关联，在第一个GRS四分位数中风险比为1.59（95%CI：1.05 - 2.41），在第四个GRS四分位数中为1.91（95%CI：1.28 - 2.86）。使用汇总统计数据，我们发现CAD与AD之间没有遗传重叠。然而，我们确实发现AD和CAD都与脂质有显著的遗传重叠，但这种重叠来自明显不同的基因簇。总之，发现CAD的遗传易感性会改变CVD与痴呆症之间的关联，很可能是通过与共同风险因素的关联。
