AIMS To study the association between an atrial fibrillation (AF) genetic risk score with prevalent AF and all-cause mortality in patients with heart failure. METHODS AND RESULTS An AF genetic risk score was calculated in 3759 European ancestry individuals (1783 with sinus rhythm, 1976 with AF) from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) by summing 97 single nucleotide polymorphism (SNP) alleles (ranging from 0-2) weighted by the natural logarithm of the relative SNP risk from the latest AF genome-wide association study. Further, we assessed AF risk variance explained by additive SNP variation, and performance of clinical or genetic risk factors, and the combination in classifying AF prevalence. AF was classified as AF or atrial flutter (AFL) at baseline electrocardiogram and/or a history of AF or AFL. The genetic risk score was associated with AF after multivariable adjustment. Odds ratio for AF prevalence per 1-unit increase genetic risk score was 2.12 (95% confidence interval 1.84-2.45, P = 2.15 × 10-24 ) in the total cohort, 2.08 (1.72-2.50, P = 1.30 × 10-14 ) in heart failure with reduced ejection fraction (HFrEF) and 2.02 (1.37-2.99, P = 4.37 × 10-4 ) in heart failure with preserved ejection fraction (HFpEF). AF-associated loci explained 22.9% of overall AF SNP heritability. Addition of the genetic risk score to clinical risk factors increased the C-index by 2.2% to 0.721. CONCLUSIONS The AF genetic risk score was associated with increased AF prevalence in HFrEF and HFpEF. Genetic variation accounted for 22.9% of overall AF SNP heritability. Addition of genetic risk to clinical risk improved model performance in classifying AF prevalence.

中文翻译：

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心力衰竭患者的遗传风险和房颤。

目的研究心力衰竭患者房颤（AF）遗传风险评分与普遍性AF与全因死亡率之间的关系。方法和结果通过对97个单核苷酸多态性（SNP）求和，从3生物学研究到慢性心力衰竭的个体化治疗（BIOSTAT-CHF）中，计算了3759名欧洲血统个体（窦性心律为1783年，房颤为AF）的AF遗传风险评分。等位基因（范围为0-2）由最新AF基因组关联研究的相对SNP风险的自然对数加权。此外，我们评估了房颤风险方差，其由累加SNP变异，临床或遗传风险因素的表现以及对房颤患病率进行分类的组合解释。在基线心电图和/或有AF或AFL病史的情况下，AF分为AF或房扑（AFL）。多变量调整后，遗传风险评分与房颤相关。总人群中每增加1个单位的遗传风险评分AF患病几率​​为2.12（95％置信区间1.84-2.45，P = 2.15×10-24），2.08（1.72-2.50，P = 1.30×10-14 ）且射血分数（HFrEF）降低的心力衰竭患者为2.02（1.37-2.99，P = 4.37×10-4）。AF相关基因座解释了22.9％的总AF SNP遗传性。将遗传风险评分添加到临床危险因素中后，C指数增加了2.2％，达到0.721。结论AF遗传风险评分与HFrEF和HFpEF的AF患病率增加有关。遗传变异占总AF SNP遗传力的22.9％。将遗传风险添加到临床风险可改善对AF患病率进行分类的模型性能。