Single-SNP GWAS of LDL on Chromosome 19: Replicating Known Associations as Motivation for Region-Level Tests

Background: Low-density lipoprotein (LDL) is a type of cholesterol linked to an increased risk of heart attack and stroke. Studies by the Global Lipids Genetics Consortium (GLGC) show that genes on Chromosome 19, such as LDLR (low-density lipoprotein receptor) and ApoE (apolipoprotein), contribute to LDL blood concentration. Chromosomal regions such as genes can be defined as genetic variants called single nucleotide polymorphisms (SNPs). To test for associations between LDL concentration and SNPs, researchers conduct genome-wide association studies (GWAS). Objectives: We conduct a single-SNP GWAS to test for associations between SNPs in Chromosome 19 and LDL concentrations. We aim to replicate known results from the GLGC. Methods: We analysed trait and covariate data from the Canadian Longitudinal Study on Aging (CLSA) and HRC panel-imputed SNP data from the CLSA version two Genomics2 dataset. Data were restricted to individuals of European ancestry, with a sample size of 19,669. We performed linear regression with Plink 2.0 for each SNP as a covariate with LDL concentration as the response. Other covariates include sex, age, age-sex interaction term, and three principal components to reflect residual population structure. Manhattan plots visualize signals of genetic association for each SNP using a genome-wide testing threshold of 510-8. Results: Chromosome 19 has 196 statistically significant SNPs out of 794,409 variants. The most significant is a SNP was located in ApoE (p-value ≈ 10-97). Conclusions: Several SNPs on Chromosome 19 are highly associated with LDL concentration. These results align with those from the GLGC, confirming our pipeline’s biological plausibility and sensitivity. We plan to perform region-level tests using software such as BigLD and RegionScan.