Cholesterol-lowering gene changes may increase the risk of c
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 cataract (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, they 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.