Genome-wide association analysis identified five novel signals near established lipid loci at HIF3A, ADAMTS3, PLTP, LCAT, and LIPG, and uncovered novel associations for rare coding variants at LIPC and LIPG with HDL subclasses.
Observational (n=8,372)
The identification of novel genetic variants associated with lipoprotein subclasses provides further insight into the molecular basis of dyslipidemia and potential therapeutic targets.
p-value: p=<5x10^-8
Lipid and lipoprotein subclasses are associated with metabolic and cardiovascular diseases, yet the genetic contributions to variability in subclass traits are not fully understood. We conducted single-variant and gene-based association tests between 15.1M variants from genome-wide and exome array and imputed genotypes and 72 lipid and lipoprotein traits in 8,372 Finns. After accounting for 885 variants at 157 previously identified lipid loci, we identified five novel signals near established loci at HIF3A, ADAMTS3, PLTP, LCAT, and LIPG. Four of the signals were identified with a low-frequency (0.005<minor allele frequency MAF<0.05) or rare (MAF<0.005) variant, including Arg123His in LCAT. Gene-based associations (P<10-10) support a role for coding variants in LIPC and LIPG with lipoprotein subclass traits. 30 established lipid-associated loci had a stronger association for a subclass trait than any conventional trait. These novel association signals provide further insight into the molecular basis of dyslipidemia and the etiology of metabolic disorders.
Davis et al. (Mon,) conducted a observational in Dyslipidemia / Lipid and lipoprotein subclasses (n=8,372). Genetic variants (common, low-frequency, and rare) vs. Reference alleles was evaluated on Association of genetic variants with 72 lipid and lipoprotein traits (p=<5x10^-8). Genome-wide association analysis identified five novel signals near established lipid loci at HIF3A, ADAMTS3, PLTP, LCAT, and LIPG, and uncovered novel associations for rare coding variants at LIPC and LIPG with HDL subclasses.