Effect of Loss-of-Function Genetic Variants in PCSK9 on Glycemic Traits, Neurocognitive Impairment, and Hepatobiliary Function
RESEARCH DESIGN AND METHODS: We identified carriers of PCSK9 pLoF in UK Biobank exome sequencing data. We assessed the aggregate effects of these variants on lipid/lipoprotein traits, which served as a positive control. Association of PCSK9 pLoF carrier status and glycemic traits, hepatobiliary function, neurocognitive traits was then evaluated as a measure for adverse effects.
RESULTS: We identified 374 individuals with 41 pLoF variants. As expected, we found that PCSK9 pLoF carriers had significantly lower LDL-C (P = 7.4 × 10-55) and apoB levels (P = 7.6 × 10-50) compared with noncarriers. However, we found no significant associations between pLoF carrier-status and glycemic traits, hepatobiliary function and neurocognitive traits (P > 0.05).
CONCLUSIONS: Our results do not support adverse effects of PCSK9 pLoF on glycemic traits, hepatobiliary function or neurocognitive traits.