Trans-Ethnic Meta-Analysis on Lipid Exome Sequencing Data
Open Access
- Author:
- Cheng, Yuhuan
- Graduate Program:
- Bioinformatics and Genomics
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- March 12, 2021
- Committee Members:
- Dajiang Liu, Thesis Advisor/Co-Advisor
George H Perry, Program Head/Chair
Laura Carrel, Committee Member
Duanping Liao, Committee Member - Keywords:
- GWAS
trans-ethnic
meta-analysis
lipids
cardiovascular disease
rare variant
whole-exome sequence - Abstract:
- Genome-wide association studies (GWAS) have provided evidence for associations between genetic variants with lipid levels in human blood that function as risk factors in cardiovascular diseases. Combined with meta-analysis, more connections between genetic variants (including both common variants and rare variants) and complex disease traits can be found in larger sample sizes. In sample sizes of up to 150,000 individuals, we applied and evaluated our proposed approach for performing a meta-analysis of DNA sequence variants association test on their exome sequencing data with six different blood lipid level traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (Non-HDL-C), triglycerides (TG), TG/HDL ratio and total cholesterol (TC). In single variant association tests, we identified 623 variants that met the significance threshold (P < 5 × 10-8), at 10 novel loci and 90 known loci, associated with one or more of four traits (HDL, LDL, TG, TC). We also identified 37 significant loci for Non-HDL trait and 30 significant loci for TG/HDL ratio trait. By comparing to other three methods, including fixed effects model, random effects model and meta-regression model, our results show that our method has an advantage in identifying significant variants, and also rare variants with lower minor allele frequency (MAF<0.01).