Increased risk-taking is a central component of bipolar disorder (BIP) and is implicated in schizophrenia (SCZ). Risky behaviours, including smoking and alcohol use, are overrepresented in both disorders and associated with poor health outcomes. Positive genetic correlations are reported but an improved understanding of the shared genetic architecture between risk phenotypes and psychiatric disorders may provide insights into underlying neurobiological mechanisms. We aimed to characterise the genetic overlap between risk phenotypes and SCZ, and BIP by estimating the total number of shared variants using the bivariate causal mixture model and identifying shared genomic loci using the conjunctional false discovery rate method. Summary statistics from genome wide association studies of SCZ, BIP, risk-taking and risky behaviours were acquired (n = 82,315–466,751). Genomic loci were functionally annotated using FUMA. Of 8.6–8.7 K variants predicted to influence BIP, 6.6 K and 7.4 K were predicted to influence risk-taking and risky behaviours, respectively. Similarly, of 10.2–10.3 K variants influencing SCZ, 9.6 and 8.8 K were predicted to influence risk-taking and risky behaviours, respectively. We identified 192 loci jointly associated with SCZ and risk phenotypes and 206 associated with BIP and risk phenotypes, of which 68 were common to both risk-taking and risky behaviours and 124 were novel to SCZ or BIP. Functional annotation implicated differential expression in multiple cortical and sub-cortical regions. In conclusion, we report extensive polygenic overlap between risk phenotypes and BIP and SCZ, identify specific loci contributing to this shared risk and highlight biologically plausible mechanisms that may underlie risk-taking in severe psychiatric disorders.

冒险行为增加是双相情感障碍 (BIP) 的核心组成部分，并且与精神分裂症 (SCZ) 有关。包括吸烟和饮酒在内的危险行为在这两种疾病中的比例过高，并且与健康状况不佳有关。据报道存在正遗传相关性，但对风险表型和精神疾病之间共享遗传结构的更好理解可能会提供对潜在神经生物学机制的见解。我们旨在通过使用双变量因果混合模型估计共享变异的总数并使用联合错误发现率方法识别共享基因组位点来表征风险表型与 SCZ 和 BIP 之间的遗传重叠。获得了 SCZ、BIP、冒险和冒险行为的全基因组关联研究的汇总统计数据（n = 82,315–466,751）。使用 FUMA 对基因组位点进行功能注释。在预测影响 BIP 的 8.6–8.7 K 变体中，预计分别有 6.6 K 和 7.4 K 影响冒险和冒险行为。同样，在影响 SCZ 的 10.2–10.3 K 变体中，预计 9.6 和 8.8 K 会分别影响冒险和冒险行为。我们确定了 192 个与 SCZ 和风险表型共同相关的基因座，以及 206 个与 BIP 和风险表型相关的基因座，其中 68 个对于冒险行为和冒险行为都是常见的，124 个对于 SCZ 或 BIP 是新的。功能注释涉及多个皮层和皮层下区域的差异表达。总之，我们报告了风险表型与 BIP 和 SCZ 之间广泛的多基因重叠，