Journal article
Gene-targeted analysis of copy number variants identifies 3 novel associations with coronary heart disease traits
SJ Costelloe, JS El-Sayed Moustafa, F Drenos, J Palmen, L Qiao, S Whiting, M Thomas, M Kivimaki, M Kumari, AD Hingorani, I Tzoulaki, J Marjo-Riitta, R Aimo, AL Hartikainen, A Pouta, RG Walters, AIF Blakemore, SE Humphries, LJM Coin, PJ Talmud
Circulation Cardiovascular Genetics | LIPPINCOTT WILLIAMS & WILKINS | Published : 2012
Abstract
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 w..
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Awarded by European Commission
Funding Acknowledgements
Drs Hingorani, Humphries, and P.J. Talmud were funded by the British Heart Foundation under RG08/014, and Dr Kumari was funded by the British Heart Foundation under PG07/133/24260. J.S.E-S. Moustafa was funded by an Imperial College Division of Medicine PhD studentship. Drs Coin and Li received funding from European Community's Seventh Framework Programme (grant No. 223367, MultiMod). Drs Kivimaki and Kumari were partially supported by the National Heart, Lung and Blood Institute (NHLBI: HL36310). The WHII study was supported by grants from the Medical Research Council; British Heart Foundation; Health and Safety Executive; Department of Health; National Heart, Lung and Blood Institute (NHLBI: HL36310), and National Institute on Aging (AG13196), US, NIH; Agency for Health Care Policy Research (HS06516); and the John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health. NFBC1966 received financial support from the Academy of Finland (project grants 104781, 120315, 129269, 1114194, 139900/24300796, Center of Excellence in Complex Disease Genetics and SALVE), University Hospital Oulu, Biocenter, University of Oulu, Finland (75617), the European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643), NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), ENGAGE project and grant agreement HEALTH-F4-2007-201413, the Medical Research Council, UK (G0500539, G0600705, G0600331, PrevMetSyn/SALVE, PS0476), and the Wellcome Trust (project grant GR069224, WT089549), UK. Replication genotyping was supported, in part, by MRC grant G0601261, Wellcome Trust grants 085301, 090532, and 083270, and Diabetes UK grants RD08/0003704 and BDA 08/0003775. The DNA extractions, sample quality controls, biobank upkeeping, and aliquoting were performed in the National Public Health Institute, Biomedicum Helsinki, Finland, and were supported financially by the Academy of Finland and Biocentrum Helsinki. Genotyping of the FCC groups had previously been funded by Genome Canada and Genome Quebec.