Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol
- Lange, Leslie A.
- Hu, Youna
- Zhang, He
- Xue, Chenyi
- Schmidt, Ellen M.
- Tang, Zheng-Zheng
- Bizon, Chris
- Lange, Ethan M.
- Smith, Joshua D.
- Turner, Emily H.
- Jun, Goo
- Kang, Hyun Min
- Peloso, Gina
- Auer, Paul
- Li, Kuo-ping
- Flannick, Jason
- Zhang, Ji
- Fuchsberger, Christian
- Gaulton, Kyle
- Lindgren, Cecilia
- Locke, Adam
- Manning, Alisa
- Sim, Xueling
- Rivas, Manuel A.
- Holmen, Oddgeir L.
- Gottesman, Omri
- Lu, Yingchang
- Ruderfer, Douglas
- Stahl, Eli A.
- Duan, Qing
- Li, Yun
- Durda, Peter
DOIAbstract
Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98th or <2nd percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, enc...
Add to ORKG