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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol
Yingchang Lu1, Martijn E T Dollé, Sandra Imholz
1Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands. kevin.lu@wur.nl
Journal of Lipid Research
|July 29, 2008
Summary
This study identified seven novel single nucleotide polymorphisms (SNPs) associated with high-density lipoprotein cholesterol (HDL-C) levels, expanding our understanding of HDL-C genetics. These findings highlight new potential targets for managing HDL-C and cardiovascular health.
Area of Science:
- Genetics
- Cardiovascular Disease Research
- Metabolic Health
Background:
- Known genetic variants explain limited variation in plasma high-density lipoprotein cholesterol (HDL-C) levels.
- Understanding genetic contributions to HDL-C is crucial for metabolic and cardiovascular health.
- Previous research identified candidate genes, but a comprehensive analysis of novel variants is needed.
Purpose of the Study:
- To identify novel single nucleotide polymorphisms (SNPs) associated with plasma HDL-C levels.
- To investigate the genetic architecture of HDL-C variation in a large cohort.
- To replicate and discover genetic associations with HDL-C metabolism.
Main Methods:
- Genotyping of 384 SNPs across 251 genes in 3,575 subjects from the Doetinchem cohort over 11 years.
- Quality control filtering to select 353 SNPs in 239 genes.
- Statistical analysis using false discovery rate (FDR) adjusted q values to assess SNP associations with HDL-C.
Main Results:
- Seven SNPs in genes including CETP, LPL, LIPC, and NRIP1 showed significant association with HDL-C (FDR_q < 0.05).
- Five additional SNPs in SC4MOL, PTPN11, ADD1, SCAND1, and MBTPS2 were associated with HDL-C (0.05 <= FDR_q <= 0.2).
- Replicated associations for known genes (CETP, LPL, LIPC, HNF4A, APOA5) and identified novel candidate SNPs for HDL-C levels.
Conclusions:
- Identified seven novel SNPs and replicated known associations related to plasma HDL-C levels.
- The findings contribute to a deeper understanding of the genetic factors influencing HDL-C.
- Newly identified SNPs warrant further investigation for their role in HDL-C metabolism and cardiovascular disease risk.
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