Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
Department of Clinical, Educational and Health Psychology, University College London, London, UK.
Sci Rep. 2023 Jun 23;13(1):10212. doi: 10.1038/s41598-023-37123-y.
Observational studies frequently report phenotypic associations between low resting heart rate (RHR) and higher levels of antisocial behaviour (ASB), although it remains unclear whether this relationship reflects causality. To triangulate evidence, we conducted two-sample univariable Mendelian randomisation (MR), multivariable MR and linkage disequilibrium score regression (LDSC) analyses. Genetic data were accessed from published genome-wide association studies (GWAS) for RHR (n = 458,835) and ASB (n = 85,359) for the univariable analyses, along with a third GWAS for heart rate variability (HRV; n = 53,174) for all other analyses. Genome-wide significant (p < 5 × 10) single-nucleotide polymorphisms associated with RHR (n = 278) were selected as instrumental variables and the outcome was a composite measure of ASB. No causal association was observed between RHR and ASB (B = - 0.0004, p = 0.841). The multivariable MR analyses including RHR and HRV also suggested no causal associations (B = 0.016, p = 0.914) and no genetic correlations between the heart rate measures and ASB were observed using LDSC (r = 0.057, p = 0.169). Sensitivity analyses suggested that our results are not likely to be affected by heterogeneity, pleiotropic effects, or reverse causation. These findings suggest that individual differences in autonomic nervous system functioning indexed by RHR are not likely to directly contribute to the development of ASB. Therefore, previously observed associations between RHR and ASB may arise from confounding, reverse causation, and/or additional study characteristics. Further causally informative longitudinal research is required to confirm our findings, and caution should be applied when using measures of RHR in interventions targeting ASB.
观察性研究经常报告静息心率 (RHR) 低与反社会行为 (ASB) 水平较高之间存在表型关联，但尚不清楚这种关系是否反映了因果关系。为了综合证据，我们进行了两样本单变量孟德尔随机化 (MR)、多变量 MR 和连锁不平衡得分回归 (LDSC) 分析。遗传数据来自已发表的 RHR（n=458835）和 ASB（n=85359）的全基因组关联研究 (GWAS)，用于单变量分析，以及用于所有其他分析的第三个 GWAS 用于心率变异性 (HRV；n=53174)。选择与 RHR 相关的全基因组显著（p<5×10）单核苷酸多态性（n=278）作为工具变量，结果是 ASB 的综合衡量标准。RHR 与 ASB 之间未观察到因果关系（B=−0.0004，p=0.841）。包括 RHR 和 HRV 的多变量 MR 分析也表明没有因果关系（B=0.016，p=0.914），并且使用 LDSC 观察到心率测量值与 ASB 之间没有遗传相关性（r=0.057，p=0.169）。敏感性分析表明，我们的结果不太可能受到异质性、多效性或反向因果关系的影响。这些发现表明，RHR 所代表的自主神经系统功能的个体差异不太可能直接导致 ASB 的发展。因此，先前观察到的 RHR 与 ASB 之间的关联可能源于混杂、反向因果关系和/或其他研究特征。需要进一步进行因果关系的纵向研究来证实我们的发现，并且在针对 ASB 的干预措施中使用 RHR 测量值时应谨慎。
