Concept, Design and Implementation of a Cardiovascular Gene-centric 50 K SNP Array for Large-scale Genomic Association Studies
View/ Open
Author
Keating, Brendan J.
Tischfield, Sam
Murray, Sarah S.
Bhangale, Tushar
Price, Thomas S.
Glessner, Joseph T.
Galver, Luana
Barrett, Jeffrey C.
Grant, Struan F. A.
Farlow, Deborah N.
Chandrupatla, Hareesh R.
Ajmal, Saad
Papanicolaou, George J.
Guo, Yiran
Li, Mingyao
DerOhannessian, Stephanie
Bailey, Swneke D.
Montpetit, Alexandre
Edmondson, Andrew C.
Taylor, Kent
Gai, Xiaowu
Wang, Susanna S.
Fornage, Myriam
Shaikh, Tamim
Groop, Leif
Boehnke, Michael
Hall, Alistair S.
Hattersley, Andrew T.
Frackelton, Edward
Patterson, Nick
Chiang, Charleston W. K.
Kim, Cecelia E.
Fabsitz, Richard R.
Ouwehand, Willem
Munroe, Patricia
Caulfield, Mark
Drake, Thomas
Boerwinkle, Eric
Whitehead, A. Stephen
Cappola, Thomas P.
Samani, Nilesh J.
Lusis, A. Jake
Schadt, Eric
Wilson, James G.
Koenig, Wolfgang
McCarthy, Mark I.
Kathiresan, Sekar
Gabriel, Stacey B.
Hakonarson, Hakon
Anand, Sonia S.
Reilly, Muredach
Engert, James C.
Nickerson, Deborah A.
Rader, Daniel J.
FitzGerald, Garret A.
Reitsma, Pieter H.
Hansen, Mark
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1371/journal.pone.0003583Metadata
Show full item recordCitation
Keating, Brendan J., Sam Tischfield, Sarah S. Murray, Tushar Bhangale, Thomas S. Price, Joseph T. Glessner, Luana Galver, et al. 2008. Concept, design and implementation of a cardiovascular gene-centric 50 K SNP array for large-scale genomic association studies. PLoS ONE 3(10): e3583.Abstract
A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a “cosmopolitan” tagging approach to capture the genetic diversity across ∼2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571995/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:8350349
Collections
- HMS Scholarly Articles [17917]
- SPH Scholarly Articles [6362]
Contact administrator regarding this item (to report mistakes or request changes)