A genome-wide association study (GWAS) identified 95 loci associated with blood lipid levels in over 100,000 individuals of European ancestry. These loci include 59 newly discovered associations, with 36 previously reported at genome-wide significance. The study found that these loci contribute to both normal and extreme lipid phenotypes and are relevant in non-European populations, including East Asians, South Asians, and African Americans. The results also show that some of these loci are associated with coronary artery disease (CAD), suggesting potential therapeutic targets. The study validated three genes—GALNT2, PPP1R3B, and TTC39B—using mouse models. The findings provide insights into the biological mechanisms of lipid metabolism and offer new opportunities for the prevention and treatment of CAD. The study also highlights the importance of genetic variation in lipid traits and its potential impact on cardiovascular health. The results emphasize the value of large-scale genetic studies in understanding complex diseases and identifying new therapeutic targets.A genome-wide association study (GWAS) identified 95 loci associated with blood lipid levels in over 100,000 individuals of European ancestry. These loci include 59 newly discovered associations, with 36 previously reported at genome-wide significance. The study found that these loci contribute to both normal and extreme lipid phenotypes and are relevant in non-European populations, including East Asians, South Asians, and African Americans. The results also show that some of these loci are associated with coronary artery disease (CAD), suggesting potential therapeutic targets. The study validated three genes—GALNT2, PPP1R3B, and TTC39B—using mouse models. The findings provide insights into the biological mechanisms of lipid metabolism and offer new opportunities for the prevention and treatment of CAD. The study also highlights the importance of genetic variation in lipid traits and its potential impact on cardiovascular health. The results emphasize the value of large-scale genetic studies in understanding complex diseases and identifying new therapeutic targets.