Statin Initiation In High Risk Patients Not To Be Delayed Du
Genotyping data and exome sequencing data of unrelated European individuals in the UK Biobank to test the association between genetically proxied inhibition of HMGCR and cataract risk. They constructed an HMGCR genetic score consisting of 5 common variants weighted by their association with low density lipoprotein cholesterol. They analyzed exome sequencing data to identify carriers of predicted loss of function mutations in HMGCR. Common and rare variants in aggregate were then tested for association with cataracts and cataract surgery. In an analysis of >402 000 individuals, a 38.7 mg/dL (1 mmol/L) reduction in low density lipoprotein C by the HMGCR genetic score was associated with higher risk for cataract (odds ratio, 1.14 [95% CI, 1.00–1.39], P=0.045) and cataract surgery (odds ratio, 1.25 [95% CI, 1.06–1.48], P=0.009). Among 169 172 individuals with HMGCR sequencing data, we identified 32 participants (0.02%), who carried a rare HMGCR predicted loss of function variant. Compared with noncarriers, heterozygous carriers of HMGCR predicted loss of function had a higher risk of developing cataracts (odds ratio, 4.54 [95% CI, 1.96–10.53], P=0.001) and cataract surgery (odds ratio, 5.27 [95% CI, 2.27–12.25], P=5.37×10^4). In exploratory analyses, we found no significant association between genetically proxied inhibition of PCSK9, NPC1L1, or circulating low density lipoprotein cholesterol levels (P>0.05 for all) and cataract risk.