Epigenetic GrimAge acceleration and cognitive impairment in bipolar disorder.
Epigenetic GrimAge acceleration and cognitive impairment in bipolar disorder.
复制标题
DOI：
10.1016/j.euroneuro.2022.06.007
复制
发表时间：
2022-09
影响因子：
5.6
通讯作者：
Fries, Gabriel R.
中科院分区：
文献类型：
--
作者：
Lima, Camila N. C.;Suchting, Robert;Scaini, Giselli;Cuellar, Valeria A.;Del Favero-Campbell, Alexandra;Walss-Bass, Consuelo;Soares, Jair C.;Quevedo, Joao;Fries, Gabriel R.
双相情感障碍（BD）以前被认为与过早衰老的临床症状有关，包括血液和大脑的表观遗传加速老化，以及与年龄相关的认知功能急剧下降。然而，双相情感障碍表观遗传衰老的临床驱动因素和认知相关性仍然未知。我们的目的是研究双相情感障碍患者和对照组表观遗传衰老加速的多种测量指标与临床、功能和认知结果之间的关系。使用 Infinium MmethylationEPIC BeadChip (Illumina) 测量了 BD 患者 (n=153) 和匹配的健康对照 (n=50) 的血液全基因组 DNA 甲基化水平。表观遗传年龄估计是使用在线工具计算的，包括最近开发的寿命预测器 GrimAge，并使用控制人口变量和血细胞比例的广义线性模型进行分析。 BD 与更大的 GrimAge 加速显着相关（AgeAccelGrim，β=0.197，p=0.009），并且在 AgeAccelGrim 和血细胞比例（CD4+ T 淋巴细胞、单核细胞、粒细胞和 B 细胞）之间发现了显着的组依赖性相互作用。在患者中，较高的 AgeAccelGrim 与多个领域的认知功能较差相关（短期情感记忆（β=-0.078，p=0.030）、短期非情感记忆（β=-0.088，p=0.018）、抑制（β=0.064，p=0.046）和问题解决（β=-0.067， p=0.034）），首次诊断患有任何情绪障碍（β=-0.076，p=0.039）或BD（β=-0.102，p=0.016）的年龄，以及当前吸烟状况（β=-0.392，p<0.001）。总体而言，我们的研究结果支持表观遗传因素对双相情感障碍患者与衰老相关的认知能力下降和过早死亡的影响，其中吸烟对该人群有重要的驱动作用。
Bipolar disorder (BD) has been previously associated with clinical signs of premature aging, including accelerated epigenetic aging in blood and brain, and a steeper age-related decline in cognitive function. However, the clinical drivers and cognitive correlates of epigenetic aging in BD are still unknown. We aimed to investigate the relationship between multiple measures of epigenetic aging acceleration with clinical, functioning, and cognitive outcomes in patients with BD and controls. Blood genome-wide DNA methylation levels were measured in BD patients (n=153) and matched healthy controls (n=50) with the Infinium MethylationEPIC BeadChip (Illumina). Epigenetic age estimates were calculated using an online tool, including the recently developed lifespan predictor GrimAge, and analyzed with generalized linear models controlling for demographic variables and blood cell proportions. BD was significantly associated with greater GrimAge acceleration (AgeAccelGrim, β=0.197, p=0.009), and significant group-dependent interactions were found between AgeAccelGrim and blood cell proportions (CD4+ T-lymphocytes, monocytes, granulocytes, and B-cells). Within patients, higher AgeAccelGrim was associated with worse cognitive function in multiple domains (short-term affective memory (β=−0.078, p=0.030), short-term non-affective memory (β=−0.088, p=0.018), inhibition (β=0.064, p=0.046), and problem solving (β=−0.067, p=0.034)), age of first diagnosis with any mood disorder (β=−0.076, p=0.039) or BD (β=−0.102, p=0.016), as well as with current smoking status (β=−0.392, p<0.001). Overall, our findings support the contribution of epigenetic factors to the aging-related cognitive decline and premature mortality reported in BD patients, with an important driving effect of smoking in this population.
登录
查看更多内容
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
39.3
作者：
Al Mamun, A;Peeters, A;Bonneux, L
通讯作者：
Bonneux, L
影响因子：
4.8
作者：
Fries, Gabriel R.;Zamzow, Madeline J.;Walss-Bass, Consuelo
通讯作者：
Walss-Bass, Consuelo
DOI：
10.1038/s41569-018-0064-2
发表时间：
2018-09
期刊：
Nature reviews. Cardiology
影响因子：
--
作者：
Ferrucci L;Fabbri E
通讯作者：
Fabbri E
影响因子：
3.3
作者：
Fusar-Poli L;Natale A;Amerio A;Cimpoesu P;Grimaldi Filioli P;Aguglia E;Amore M;Serafini G;Aguglia A
通讯作者：
Aguglia A