IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0020133.html
   My bibliography  Save this article

From SNPs to Genes: Disease Association at the Gene Level

Author

Listed:
  • Benjamin Lehne
  • Cathryn M Lewis
  • Thomas Schlitt

Abstract

Interpreting Genome-Wide Association Studies (GWAS) at a gene level is an important step towards understanding the molecular processes that lead to disease. In order to incorporate prior biological knowledge such as pathways and protein interactions in the analysis of GWAS data it is necessary to derive one measure of association for each gene. We compare three different methods to obtain gene-wide test statistics from Single Nucleotide Polymorphism (SNP) based association data: choosing the test statistic from the most significant SNP; the mean test statistics of all SNPs; and the mean of the top quartile of all test statistics. We demonstrate that the gene-wide test statistics can be controlled for the number of SNPs within each gene and show that all three methods perform considerably better than expected by chance at identifying genes with confirmed associations. By applying each method to GWAS data for Crohn's Disease and Type 1 Diabetes we identified new potential disease genes.

Suggested Citation

  • Benjamin Lehne & Cathryn M Lewis & Thomas Schlitt, 2011. "From SNPs to Genes: Disease Association at the Gene Level," PLOS ONE, Public Library of Science, vol. 6(6), pages 1-10, June.
    • Handle: RePEc:plo:pone00:0020133
    DOI: 10.1371/journal.pone.0020133
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0020133
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0020133&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0020133?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yasunori Ogura & Denise K. Bonen & Naohiro Inohara & Dan L. Nicolae & Felicia F. Chen & Richard Ramos & Heidi Britton & Thomas Moran & Reda Karaliuskas & Richard H. Duerr & Jean-Paul Achkar & Steven R, 2001. "A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease," Nature, Nature, vol. 411(6837), pages 603-606, May.
    2. Ayellet V Segrè & DIAGRAM Consortium & MAGIC investigators & Leif Groop & Vamsi K Mootha & Mark J Daly & David Altshuler, 2010. "Common Inherited Variation in Mitochondrial Genes Is Not Enriched for Associations with Type 2 Diabetes or Related Glycemic Traits," PLOS Genetics, Public Library of Science, vol. 6(8), pages 1-19, August.
    3. Soumya Raychaudhuri & Robert M Plenge & Elizabeth J Rossin & Aylwin C Y Ng & International Schizophrenia Consortium & Shaun M Purcell & Pamela Sklar & Edward M Scolnick & Ramnik J Xavier & David Altsh, 2009. "Identifying Relationships among Genomic Disease Regions: Predicting Genes at Pathogenic SNP Associations and Rare Deletions," PLOS Genetics, Public Library of Science, vol. 5(6), pages 1-15, June.
    4. B. Devlin & Kathryn Roeder, 1999. "Genomic Control for Association Studies," Biometrics, The International Biometric Society, vol. 55(4), pages 997-1004, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Joshua C Randall & Thomas W Winkler & Zoltán Kutalik & Sonja I Berndt & Anne U Jackson & Keri L Monda & Tuomas O Kilpeläinen & Tõnu Esko & Reedik Mägi & Shengxu Li & Tsegaselassie Workalemahu & Mary F, 2013. "Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits," PLOS Genetics, Public Library of Science, vol. 9(6), pages 1-19, June.
    2. Lei Zhang & Yu-Fang Pei & Jian Li & Christopher J Papasian & Hong-Wen Deng, 2009. "Univariate/Multivariate Genome-Wide Association Scans Using Data from Families and Unrelated Samples," PLOS ONE, Public Library of Science, vol. 4(8), pages 1-12, August.
    3. Dominic Holland & Oleksandr Frei & Rahul Desikan & Chun-Chieh Fan & Alexey A Shadrin & Olav B Smeland & V S Sundar & Paul Thompson & Ole A Andreassen & Anders M Dale, 2020. "Beyond SNP heritability: Polygenicity and discoverability of phenotypes estimated with a univariate Gaussian mixture model," PLOS Genetics, Public Library of Science, vol. 16(5), pages 1-30, May.
    4. Vincent Michaud & Eulalie Lasseaux & David J. Green & Dave T. Gerrard & Claudio Plaisant & Tomas Fitzgerald & Ewan Birney & Benoît Arveiler & Graeme C. Black & Panagiotis I. Sergouniotis, 2022. "The contribution of common regulatory and protein-coding TYR variants to the genetic architecture of albinism," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    5. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Parsa Akbari & Dragana Vuckovic & Luca Stefanucci & Tao Jiang & Kousik Kundu & Roman Kreuzhuber & Erik L. Bao & Janine H. Collins & Kate Downes & Luigi Grassi & Jose A. Guerrero & Stephen Kaptoge & Ju, 2023. "A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    7. Gang Zheng & Zhaohai Li & Mitchell H. Gail & Joseph L. Gastwirth, 2010. "Impact of Population Substructure on Trend Tests for Genetic Case–Control Association Studies," Biometrics, The International Biometric Society, vol. 66(1), pages 196-204, March.
    8. Chao Lu & Jun Yang & Weilai Yu & Dejian Li & Zun Xiang & Yiming Lin & Chaohui Yu, 2015. "Association between 25(OH)D Level, Ultraviolet Exposure, Geographical Location, and Inflammatory Bowel Disease Activity: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 10(7), pages 1-16, July.
    9. Sandosh Padmanabhan & Olle Melander & Toby Johnson & Anna Maria Di Blasio & Wai K Lee & Davide Gentilini & Claire E Hastie & Cristina Menni & Maria Cristina Monti & Christian Delles & Stewart Laing & , 2010. "Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension," PLOS Genetics, Public Library of Science, vol. 6(10), pages 1-11, October.
    10. Junjiao Feng & Liang Zhang & Chunhui Chen & Jintao Sheng & Zhifang Ye & Kanyin Feng & Jing Liu & Ying Cai & Bi Zhu & Zhaoxia Yu & Chuansheng Chen & Qi Dong & Gui Xue, 2022. "A cognitive neurogenetic approach to uncovering the structure of executive functions," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    11. Jakris Eu-ahsunthornwattana & E Nancy Miller & Michaela Fakiola & Wellcome Trust Case Control Consortium 2 & Selma M B Jeronimo & Jenefer M Blackwell & Heather J Cordell, 2014. "Comparison of Methods to Account for Relatedness in Genome-Wide Association Studies with Family-Based Data," PLOS Genetics, Public Library of Science, vol. 10(7), pages 1-20, July.
    12. Jianzhong Ma & Christopher I Amos, 2010. "Theoretical Formulation of Principal Components Analysis to Detect and Correct for Population Stratification," PLOS ONE, Public Library of Science, vol. 5(9), pages 1-14, September.
    13. Claire L Simpson & Robert Wojciechowski & Konrad Oexle & Federico Murgia & Laura Portas & Xiaohui Li & Virginie J M Verhoeven & Veronique Vitart & Maria Schache & S Mohsen Hosseini & Pirro G Hysi & Le, 2014. "Genome-Wide Meta-Analysis of Myopia and Hyperopia Provides Evidence for Replication of 11 Loci," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-19, September.
    14. David Lamparter & Daniel Marbach & Rico Rueedi & Zoltán Kutalik & Sven Bergmann, 2016. "Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics," PLOS Computational Biology, Public Library of Science, vol. 12(1), pages 1-20, January.
    15. Niina Sandholm & Rany M Salem & Amy Jayne McKnight & Eoin P Brennan & Carol Forsblom & Tamara Isakova & Gareth J McKay & Winfred W Williams & Denise M Sadlier & Ville-Petteri Mäkinen & Elizabeth J Swa, 2012. "New Susceptibility Loci Associated with Kidney Disease in Type 1 Diabetes," PLOS Genetics, Public Library of Science, vol. 8(9), pages 1-13, September.
    16. Matthieu Bouaziz & Christophe Ambroise & Mickael Guedj, 2011. "Accounting for Population Stratification in Practice: A Comparison of the Main Strategies Dedicated to Genome-Wide Association Studies," PLOS ONE, Public Library of Science, vol. 6(12), pages 1-13, December.
    17. Aditi Shendre & Howard W Wiener & Marguerite R Irvin & Bradley E Aouizerat & Edgar T Overton & Jason Lazar & Chenglong Liu & Howard N Hodis & Nita A Limdi & Kathleen M Weber & Stephen J Gange & Degui , 2017. "Genome-wide admixture and association study of subclinical atherosclerosis in the Women’s Interagency HIV Study (WIHS)," PLOS ONE, Public Library of Science, vol. 12(12), pages 1-23, December.
    18. Li Shaoyu & Lu Qing & Fu Wenjiang & Romero Roberto & Cui Yuehua, 2009. "A Regularized Regression Approach for Dissecting Genetic Conflicts that Increase Disease Risk in Pregnancy," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 8(1), pages 1-30, October.
    19. Warrington Nicole M. & Tilling Kate & Howe Laura D. & Paternoster Lavinia & Pennell Craig E. & Wu Yan Yan & Briollais Laurent, 2014. "Robustness of the linear mixed effects model to error distribution assumptions and the consequences for genome-wide association studies," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 13(5), pages 567-587, October.
    20. Wang, Linglu & Li, Qizhai & Li, Zhaohai & Zheng, Gang, 2011. "Bayes factors in the presence of population stratification," Statistics & Probability Letters, Elsevier, vol. 81(7), pages 836-841, July.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0020133. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.