Association of polygenic risk scores with low-density lipoprotein cholesterol levels and control: findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

The HCHS/SOL study examined the use of polygenic risk scores (PRS) to predict low-density lipoprotein cholesterol (LDL) levels and control among 11,669 Hispanic and Latino adults aged 18-74 years. Researchers tested twenty different PRS and found that a score developed using the PolyFun-pred method achieved the greatest improvement in predicting LDL levels with an R2 increase of 0.114 for the full sample. For each standard deviation increase in PRS, LDL levels increased by 3 to 14 mg/dL. Among 1,323 statin users, the likelihood of LDL control significantly decreased with increasing PRS, with differences varying between individual PRS and groups with different genetic ancestry. The researchers concluded that polygenic risk scores prioritizing functional annotations demonstrate superior performance for predicting LDL levels across Hispanic and Latino subgroups, but further development is needed before clinical application in diverse populations.