Gene-targeted analysis of copy number variants identifies 3 novel associations with coronary heart disease traits

Seán J Costelloe, Julia S El-Sayed Moustafa, Fotios Drenos, Jutta Palmen, Qiao Li, Li Qiao, Stephen Whiting, Michael Thomas, Mika Kivimaki, Meena Kumari, Aroon D Hingorani, Ioanna Tzoulaki, Marjo-Riitta Järvelin, Järvelin Marjo-Riitta, Aimo Ruokonen, Ruokonen Aimo, Anna-Liisa Hartikainen, Anneli Pouta, Robin G Walters, Alexandra I F BlakemoreSteve E Humphries, Lachlan J M Coin, Philippa J Talmud

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)


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 use of the cnvHap algorithm for CNV detection, using data for 2500 men from the Second Northwick Park Heart Study (NPHS-II). An Illumina custom chip, including 722 single-nucleotide polymorphisms covering 76 coronary heart disease-trait genes, was used. Common CNVs were significantly associated (at P<0.05, after correction) with coronary heart disease phenotypes in 5 genes. Novel associations of CNVs in toll-like receptor-4 with apolipoprotein AI were replicated (P<0.05) in the Whitehall II cohort (4887 subjects), whereas newly described associations of CNVs in sterol regulatory element-binding protein with apolipoprotein AI and associations of interleukin-6 signal transducer with apolipoprotein B were replicated in the data from 3546 subjects from the North Finnish Birth Cohort 1966 (P<0.05).

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 coronary heart disease risk phenotypes. However, the functional basis for these associations requires further substantiation.

Original languageEnglish
Pages (from-to)555-60
Number of pages6
JournalCirculation: Cardiovascular Genetics
Issue number5
Publication statusPublished - 1 Oct 2012


  • Algorithms
  • Apolipoprotein A-I
  • Apolipoproteins B
  • Cohort Studies
  • Coronary Disease
  • DNA Copy Number Variations
  • Genome, Human
  • Genotype
  • Humans
  • Interleukin-6
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Sterol Regulatory Element Binding Protein 1
  • Toll-Like Receptor 4
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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