To evaluate the association between PCSK9 predicted loss-of-function (pLoF) variants and glycemic traits, hepatobiliary function, and neurocognitive traits.

We identified carriers of PCSK9 pLoF variants in UK Biobank exome sequencing data. We assessed the aggregate effects of these variants on lipid and lipoprotein traits, which served as a positive control. Association of PCSK9 pLoF carrier status and glycemic traits, hepatobiliary function, and neurocognitive traits was then evaluated as a measure for adverse effects.

We identified 374 individuals with 41 pLoF variants. As expected, we found that PCSK9 pLoF carriers had significantly lower LDL cholesterol C levels (P = 7.4 x 10^–55) and apolipoprotein B levels (P = 7.6 x 10^–50) than did noncarriers. However, we found no significant associations between pLoF carrier status and glycemic traits, hepatobiliary function, and neurocognitive traits (P > 0.05).

Our results do not support adverse effects of PCSK9 pLoF variants on glycemic traits, hepatobiliary function, or neurocognitive traits.

评估PCSK9预测功能丧失 (pLoF) 变异与血糖特征、肝胆功能和神经认知特征之间的关联。

我们在 UK Biobank 外显子组测序数据中发现了PCSK9 pLoF 变体的携带者。我们评估了这些变体对脂质和脂蛋白性状的总体影响，作为阳性对照。然后评估PCSK9 pLoF 携带者状态与血糖特征、肝胆功能和神经认知特征的关联，作为衡量不良反应的指标。

我们确定了 374 名具有 41 个 pLoF 变体的个体。正如预期的那样，我们发现PCSK9 pLoF 携带者的 LDL 胆固醇 C 水平 ( P = 7.4 x 10 ^–55 ) 和载脂蛋白 B 水平 ( P = 7.6 x 10 ^–50 ) 显着低于非携带者。然而，我们发现 pLoF 携带者状态与血糖特征、肝胆功能和神经认知特征之间没有显着关联（P > 0.05）。

我们的结果不支持PCSK9 pLoF 变异对血糖特征、肝胆功能或神经认知特征的不利影响。