BACKGROUND: Though epidemiological studies show increased cardiovascular disease (CVD) risks among individuals with psychiatric disorders, findings on sex differences in comorbidity have been inconsistent. METHODS: This genetic epidemiology study examined the sex-specific association between the genetic risk of 3 psychiatric disorders (major depression [MD], schizophrenia, and bipolar disorder), estimated using polygenic scores (PGSs), and risks of 3 CVDs (atrial fibrillation [AF], coronary artery disease [CAD], and heart failure [HF]) in 345 169 European-ancestry individuals (UK Biobank), with analyses replicated in an independent BioVU cohort (n=49 057). Mediation analysis was conducted to determine whether traditional CVD risk factors could explain any observed sex difference. RESULTS: In the UK Biobank, a 1-SD increase in PGS MD was significantly associated with the incident risks of all 3 CVDs in females after multiple testing corrections (hazard ratio [HR] AF-female =1.04 [95% CI, 1.02–1.06]; P =1.5×10 − 4 ; HR CAD-female =1.07 [95% CI, 1.04–1.11]; P =2.6×10 − 6 ; and HR HF-female =1.09 [95% CI, 1.06–1.13]; P =9.7×10 − 10 ), but not in males. These female-specific associations remained even in the absence of any psychiatric disorder diagnosis or psychiatric medication use. Although mediation analysis demonstrated that the association between PGS MD and CVDs in females was partly mediated by baseline body mass index, hypercholesterolemia, hypertension, and smoking, these risk factors did not explain the higher risk compared with males. The association between PGS MD and CAD was consistent between females who were premenopausal and postmenopausal at baseline, while the association with AF and HF was only observed in the baseline postmenopausal cohort. No significant association with CVD risks was observed for the PGS of schizophrenia or bipolar disorder. The female-specific positive association of PGS MD with CAD risk was replicated in BioVU. CONCLUSIONS: Genetic predisposition to MD confers a greater risk of CVDs in females versus males, even in the absence of any depression diagnosis. This study warrants further investigation into whether genetic predisposition to depression could be useful for improving cardiovascular risk prediction, especially in women.

Jiayue-Clara Jiang

Kritika Singh

Rachana Nitin

Lea K. Davis

Naomi R. Wray

Sonia Shah

Circulation Genomic and Precision Medicine

流通：基因组学和精准医学考虑所有类型的原始研究文章，包括在人类受试者、实验动物、体外和计算机中进行的研究。文章可能包括以下研究：临床遗传学应用于单基因或寡基因心血管疾病的诊断和管理；复杂心血管疾病的分子基础，包括全基因组关联研究、基于外显子组和基因组测序的关联研究、编码变异关联研究、遗传连锁研究、表观基因组学、转录组学、蛋白质组学、代谢组学和宏基因组学；将电子健康记录数据或患者生成的数据与上述任何方法（包括表型关联研究）或环境或生活方式因素相结合；药物基因组学；基因表达调控；基因治疗和治疗性基因组编辑；心血管疾病诊断和管理的系统生物学方法；进行上述任何研究的新方法；以及精准医学的新应用。最重要的是，我们寻求与人类心血管生物学和疾病相关的研究。

The journal "Circulation. Genomic and Precision Medicine" encompasses all types of original research articles, including studies conducted in human subjects, experimental animals, in vitro, and computational settings. Articles may cover the following research areas: clinical genetics applications in the diagnosis and management of single-gene or polygenic cardiovascular diseases; the molecular basis of complex cardiovascular diseases, including genome-wide association studies, exome and genome sequencing association studies, coding variant association studies, genetic linkage studies, epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics; integration of electronic health record data or patient-generated data with any of the aforementioned methods (including phenotype association studies) or environmental and lifestyle factors; pharmacogenomics; gene expression regulation; gene therapy and therapeutic genome editing; systems biology approaches to the diagnosis and management of cardiovascular diseases; novel methods for conducting any of the above research; and new applications of precision medicine. Importantly, we seek research related to human cardiovascular biology and disease.

《Circulation. Genomic and precision medicine》期刊涵盖所有类型的原创研究文章，包括在人类受试者、实验动物、体外实验和计算机模拟中进行的研究。文章可能涉及以下研究领域：临床遗传学在单基因或多基因心血管疾病的诊断和管理中的应用；复杂心血管疾病的分子基础，包括全基因组关联研究、外显子组和基因组测序的关联研究、编码变异关联研究、遗传连锁研究、表观基因组学、转录组学、蛋白质组学、代谢组学和宏基因组学；将电子健康记录数据或患者生成的数据与上述任何方法（包括表型关联研究）或环境和生活方式因素相结合；药物基因组学；基因表达调控；基因治疗和治疗性基因组编辑；心血管疾病诊断和管理的系统生物学方法；进行上述任何研究的新方法；以及精准医学的新应用。我们特别关注与人类心血管生物学和疾病相关的研究。

Category	Quartile
医学	2
医学, 遗传学	1
医学, 心脏和心血管系统	2

Sex-Specific Association Between Genetic Risk of Psychiatric Disorders and Cardiovascular Diseases

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Journal Info

Category	Quartile
GENETICS & HEREDITY	1