People with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. Previous studies report cardiometabolic abnormalities in BPD, but their shared aetiology remains poorly understood. This study examined the phenotypic associations and shared genetic aetiology between BPD and various cardiometabolic traits.

In a subset of the UK Biobank sample (N = 61 508) we investigated phenotypic associations between BPD (ncases = 4186) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine shared genetic aetiology in European ancestry, polygenic risk scores (PRS) and genetic correlations were calculated between BPD and cardiometabolic traits.

Several traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin, low systolic blood pressure, high body mass index, high waist-to-hip ratio; and stroke, coronary artery disease and type 2 diabetes diagnosis. BPD was associated with higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease and type 2 diabetes. Shared genetic aetiology persisted for coronary artery disease, when correcting PRS associations for cardiometabolic base phenotypes. Associations were not replicated using genetic correlations.

This large study identified increased phenotypic cardiometabolic abnormalities in BPD participants. It is found that the comorbidity of coronary artery disease may be based on shared genetic aetiology. These results motivate hypothesis-driven research to consider individual cardiometabolic traits rather than a composite metabolic syndrome when attempting to disentangle driving mechanisms of cardiometabolic abnormalities in BPD.

双相情感障碍 (BPD) 患者更容易过早死亡，部分原因是合并的心脏代谢特征。先前的研究报告了 BPD 患者的心脏代谢异常，但其共同的病因仍知之甚少。本研究探讨了 BPD 与各种心脏代谢特征之间的表型关联和共同的遗传病因学。

在英国生物银行样本的子集中 ( N = 61 508)，我们研究了 BPD（ n例= 4186）与心脏代谢特征之间的表型关联，以生物标志物、人体测量特征和心脏代谢疾病为代表。为了确定欧洲血统的共同遗传病因，计算了 BPD 和心脏代谢特征之间的多基因风险评分 (PRS) 和遗传相关性。

一些特征与 BPD 风险增加显着相关，即低总胆固醇、低高密度脂蛋白胆固醇、高甘油三酯、高糖化血红蛋白、低收缩压、高体重指数、高腰臀比；以及中风​​、冠状动脉疾病和2型糖尿病的诊断。 BPD 与甘油三酯、腰臀比、冠状动脉疾病和 2 型糖尿病的多基因风险较高相关。当纠正 PRS 与心脏代谢基础表型的关联时，冠状动脉疾病的共同遗传病因学仍然存在。未使用遗传相关性来复制关联。

这项大型研究发现 BPD 参与者的表型心脏代谢异常有所增加。研究发现，冠状动脉疾病的合并症可能基于共同的遗传病因。这些结果促使假设驱动的研究在试图解开 BPD 心脏代谢异常的驱动机制时考虑个体心脏代谢特征，而不是复合代谢综合征。