Principles for the post-GWAS functional characterization of cancer risk loci

Matthew L. Freedman; Alvaro N.A. Monteiro; Simon A. Gayther; Gerhard A. Coetzee; Angela Risch; Christoph Plass; Graham Casey; Mariella De Biasi; Chris Carlson; David Duggan; Michael James; Pengyuan Liu; Jay W. Tichelaar; Haris G. Vikis; Ming You; Ian G. Mills

doi:10.1038/ng.840

Principles for the post-GWAS functional characterization of cancer risk loci

Matthew L. Freedman, Alvaro N.A. Monteiro, Simon A. Gayther, Gerhard A. Coetzee, Angela Risch, Christoph Plass, Graham Casey, Mariella De Biasi, Chris Carlson, David Duggan, Michael James, Pengyuan Liu, Jay W. Tichelaar, Haris G. Vikis, Ming You, Ian G. Mills

Research output: Contribution to journal › Review article › peer-review

357 Scopus citations

Original language	English (US)
Pages (from-to)	513-518
Number of pages	6
Journal	Nature Genetics
Volume	43
Issue number	6
DOIs	https://doi.org/10.1038/ng.840
State	Published - Jun 2011

ASJC Scopus subject areas

Genetics

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10.1038/ng.840

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@article{889cba159b6f43918196d3382091dce0,

title = "Principles for the post-GWAS functional characterization of cancer risk loci",

author = "Freedman, {Matthew L.} and Monteiro, {Alvaro N.A.} and Gayther, {Simon A.} and Coetzee, {Gerhard A.} and Angela Risch and Christoph Plass and Graham Casey and {De Biasi}, Mariella and Chris Carlson and David Duggan and Michael James and Pengyuan Liu and Tichelaar, {Jay W.} and Vikis, {Haris G.} and Ming You and Mills, {Ian G.}",

note = "Funding Information: We would like to thank F. Bunz and all the members of the NIH Post-Genome Wide Association Initiative for helpful discussions and, in particular, I. Tomlinson (Wellcome Trust Centre for Human Genetics, Oxford). The contributing groups are supported by funding made available through the NIH Post-Genome Wide Association Initiative in response to Call (http://grants.nih.gov./grants/ oer.htm). This Call sustains research across five cancer organ sites (prostate: 1U19CA148537-01; breast: 1U19CA148065-01; ovarian: 1U19CA148112-01; colorectal: 1U19CA148107-01; and lung: 1U19CA148127-01). For further information on this Initiative, please refer to the website: (http://epi.grants.cancer. gov/). In addition, this article is the product of the first attempt to engage the entire scientific community in the drafting of a scientific paper through open-access websites. We would like to thank R. Hoffmann at WikiGenes for hosting the pre-submission version of this submission (http://www.wikigenes.org/e/ pub/e/84.html) and his unstinting energy and enthusiasm for this project and also Nature Precedings for hosting the same version (http://precedings.nature.com/ documents/5162/version/1). Funding Information: Many of the initial successful eQTL studies relied on available lymphoblastoid cell lines39,50. More recently, eQTL studies have been performed in primary human tissues and have shown that at least some associations are tissue specific40,42,51. Although large sample sizes are needed in order to achieve sufficient power to detect eQTL associations, they are typically smaller than those used in GWAS to identify risk alleles. Consequently, comprehensive biobanks of normal tissues will need to be established to evaluate expression differences between the different alleles of a SNP. Establishing such biobanks will be a major part of the challenge; whereas extensive efforts within the cancer research community have established tumor tissue biorepositories, it has been less common to do so for normal tissues from the cells representing the origin of cancers. This issue is particularly problematic for tumor subtypes in which the cell of origin is still debated. This challenge is now being recognized and addressed through funding initiatives such as the {\textquoteleft}Genotype-Tissue Expression (GTEx){\textquoteright} supported by the US National Institutes of Health Common Fund.",

year = "2011",

month = jun,

doi = "10.1038/ng.840",

language = "English (US)",

volume = "43",

pages = "513--518",

journal = "Nature Genetics",

issn = "1061-4036",

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TY - JOUR

T1 - Principles for the post-GWAS functional characterization of cancer risk loci

AU - Freedman, Matthew L.

AU - Monteiro, Alvaro N.A.

AU - Gayther, Simon A.

AU - Coetzee, Gerhard A.

AU - Risch, Angela

AU - Plass, Christoph

AU - Casey, Graham

AU - De Biasi, Mariella

AU - Carlson, Chris

AU - Duggan, David

AU - James, Michael

AU - Liu, Pengyuan

AU - Tichelaar, Jay W.

AU - Vikis, Haris G.

AU - You, Ming

AU - Mills, Ian G.

N1 - Funding Information: We would like to thank F. Bunz and all the members of the NIH Post-Genome Wide Association Initiative for helpful discussions and, in particular, I. Tomlinson (Wellcome Trust Centre for Human Genetics, Oxford). The contributing groups are supported by funding made available through the NIH Post-Genome Wide Association Initiative in response to Call (http://grants.nih.gov./grants/ oer.htm). This Call sustains research across five cancer organ sites (prostate: 1U19CA148537-01; breast: 1U19CA148065-01; ovarian: 1U19CA148112-01; colorectal: 1U19CA148107-01; and lung: 1U19CA148127-01). For further information on this Initiative, please refer to the website: (http://epi.grants.cancer. gov/). In addition, this article is the product of the first attempt to engage the entire scientific community in the drafting of a scientific paper through open-access websites. We would like to thank R. Hoffmann at WikiGenes for hosting the pre-submission version of this submission (http://www.wikigenes.org/e/ pub/e/84.html) and his unstinting energy and enthusiasm for this project and also Nature Precedings for hosting the same version (http://precedings.nature.com/ documents/5162/version/1). Funding Information: Many of the initial successful eQTL studies relied on available lymphoblastoid cell lines39,50. More recently, eQTL studies have been performed in primary human tissues and have shown that at least some associations are tissue specific40,42,51. Although large sample sizes are needed in order to achieve sufficient power to detect eQTL associations, they are typically smaller than those used in GWAS to identify risk alleles. Consequently, comprehensive biobanks of normal tissues will need to be established to evaluate expression differences between the different alleles of a SNP. Establishing such biobanks will be a major part of the challenge; whereas extensive efforts within the cancer research community have established tumor tissue biorepositories, it has been less common to do so for normal tissues from the cells representing the origin of cancers. This issue is particularly problematic for tumor subtypes in which the cell of origin is still debated. This challenge is now being recognized and addressed through funding initiatives such as the ‘Genotype-Tissue Expression (GTEx)’ supported by the US National Institutes of Health Common Fund.

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DO - 10.1038/ng.840

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Principles for the post-GWAS functional characterization of cancer risk loci

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