Gene-Targeted Analysis of Copy Number Variants Identifies Three Novel Associations with Coronary Heart Disease Traits
Background—Copy number variants (CNVs) are a major form of genomic variation which may be implicated in complex disease phenotypes. However, investigation of the role of CNVs in coronary heart disease (CHD) traits has been limited.
Methods and Results—We examined the utility of the cnvHap algorithm for CNV detection, using data for 2500 men from the Northwick Park Heart Study II (NPHS-II). An Illumina custom chip including 722 single nucleotide polymorphisms covering 76 CHD-trait genes was employed. Common CNVs were significantly associated (at P < 0.05, after correction) with CHD phenotypes in five genes. Novel associations of CNVs in TLR4 with apolipoprotein AI (apoAI) were replicated (P < 0.05) in the Whitehall II (WHII) cohort (4887 subjects), while newly described associations of CNVs in SREBP1 with apolipoprotein AI and associations of IL-6ST with apolipoprotein B were replicated in data from 3546 subjects from the North Finnish Birth Cohort 1996 (NFBC1966), (P < 0.05) while was replicated in NFBC1966.
Conclusions—This study supports the use of CNV detection algorithms such as cnvHap as potential tools for the identification of novel CNVs, some of which show significant association and replication with CHD risk phenotypes. However, the functional basis for these associations requires further substantiation.
- cardiovascular disease risk factors
- cardiovascular diseases
- genetic association
- high-density lipoprotein cholesterol
- Received August 16, 2011.
- Accepted August 13, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited