Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines


Although pioneered by human geneticists as a potential solution to the challenging problem of finding the genetic basis of common human diseases1,2, genome-wide association (GWA) studies have, owing to advances in genotyping and sequencing technology, become an obvious general approach for studying the genetics of natural variation and traits of agricultural importance. They are particularly useful when inbred lines are available, because once these lines have been genotyped they can be phenotyped multiple times, making it possible (as well as extremely cost effective) to study many different traits in many different environments, while replicating the phenotypic measurements to reduce environmental noise. Here we demonstrate the power of this approach by carrying out a GWA study of 107 phenotypes in Arabidopsis thaliana, a widely distributed, predominantly self-fertilizing model plant known to harbour considerable genetic variation for many adaptively important traits3. Our results are dramatically different from those of human GWA studies, in that we identify many common alleles of major effect, but they are also, in many cases, harder to interpret because confounding by complex genetics and population structure make it difficult to distinguish true associations from false. However, a-priori candidates are significantly over-represented among these associations as well, making many of them excellent candidates for follow-up experiments. Our study demonstrates the feasibility of GWA studies in A. thaliana and suggests that the approach will be appropriate for many other organisms.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The number of associations identified using different P -value thresholds for each phenotype.
Figure 2: GWA analysis of hypersensitive response to the bacterial elicitor AvrRpm1.
Figure 3: Candidate SNPs are over-represented among strong associations.
Figure 4: Association with FLC expression at the top of chromosome 4 near FRI.

Similar content being viewed by others


  1. Hirschhorn, J. N. & Daly, M. J. Genome-wide association studies for common diseases and complex traits. Nature Rev. Genet. 6, 95–108 (2005)

    Article  CAS  Google Scholar 

  2. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007)

  3. Koornneef, M., Alonso-Blanco, C. & Vreugdenhil, D. Naturally occurring genetic variation in Arabidopsis thaliana . Annu. Rev. Plant Biol. 55, 141–172 (2004)

    Article  CAS  Google Scholar 

  4. Nordborg, M. et al. The pattern of polymorphism in Arabidopsis thaliana . PLoS Biol. 3, e196 (2005)

    Article  Google Scholar 

  5. Shindo, C. et al. Role of FRIGIDA and FLC in determining variation in flowering time of Arabidopsis thaliana . Plant Physiol. 138, 1163–1173 (2005)

    Article  CAS  Google Scholar 

  6. Kim, S. et al. Recombination and linkage disequilibrium in Arabidopsis thaliana . Nature Genet. 39, 1151–1155 (2007)

    Article  CAS  Google Scholar 

  7. Nordborg, M. et al. The extent of linkage disequilibrium in Arabidopsis thaliana . Nature Genet. 30, 190–193 (2002)

    Article  CAS  Google Scholar 

  8. Aranzana, M. J. et al. Genome-wide association mapping in Arabidopsis identifies previously known flowering time and pathogen resistance genes. PLoS Genet. 1, e60 (2005)

    Article  Google Scholar 

  9. Zhao, K. et al. An Arabidopsis example of association mapping in structured samples. PLoS Genet. 3, e4 (2007)

    Article  Google Scholar 

  10. Pritchard, J. K., Stephens, M., Rosenberg, N. A. & Donnelly, P. Association mapping in structured populations. Am. J. Hum. Genet. 67, 170–181 (2000)

    Article  CAS  Google Scholar 

  11. Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nature Genet. 38, 904–909 (2006)

    Article  CAS  Google Scholar 

  12. Yu, J. et al. A unified mixed-model method for association mapping that accounts for multiple levels of relatedness. Nature Genet. 38, 203–208 (2005)

    Article  Google Scholar 

  13. Kang, H. M. et al. Efficient control of population structure in model organism association mapping. Genetics 178, 1709–1723 (2008)

    Article  Google Scholar 

  14. Grant, M. R. et al. Structure of the Arabidopsis RPM1 gene enabling dual-specificity disease resistance. Science 269, 843–846 (1995)

    Article  ADS  CAS  Google Scholar 

  15. Johanson, U. et al. Molecular analysis of FRIGIDA, a major determinant of natural variation in Arabidopsis flowering time. Science 290, 344–347 (2000)

    Article  ADS  CAS  Google Scholar 

  16. Toomajian, C. et al. A non-parametric test reveals selection for rapid flowering in the Arabidopsis genome. PLoS Biol. 4, e137 (2006)

    Article  Google Scholar 

  17. Michaels, S. D. & Amasino, R. M. FLOWERING LOCUS C encodes a novel MADS domain protein that acts as a repressor of flowering. Plant Cell 11, 949–956 (1999)

    Article  CAS  Google Scholar 

  18. Bentsink, L., Jowett, J., Hanhart, C. J. & Koornneef, M. Cloning of DOG1, a quantitative trait locus controlling seed dormancy in Arabidopsis . Proc. Natl Acad. Sci. USA 103, 17042–17047 (2006)

    Article  ADS  CAS  Google Scholar 

  19. Rus, A. et al. Natural variants of AtHKT1 enhance Na+ accumulation in two wild populations of Arabidopsis . PLoS Genet. 2, e210 (2006)

    Article  Google Scholar 

  20. Baxter, I. et al. Variation in molybdenum content across broadly distributed populations of Arabidopsis thaliana is controlled by a mitochondrial molybdenum transporter (MOT1). PLoS Genet. 4, e1000004 (2008)

    Article  Google Scholar 

  21. Hilscher, J., Schlötterer, C. & Hauser, M.-T. A single amino acid replacement in ETC2 acts as major modifier of trichome patterning in natural Arabidopsis populations. Curr. Biol. 19, 1747–1751 (2009)

    Article  CAS  Google Scholar 

  22. Lu, H., Rate, D. N., Song, J. T. & Greenberg, J. T. ACD6, a novel ankyrin protein, is a regulator and an effector of salicylic acid signaling in the Arabidopsis defense response. Plant Cell 15, 2408–2420 (2003)

    Article  CAS  Google Scholar 

  23. Manolio, T. A. et al. Finding the missing heritability of complex diseases. Nature 461, 747–753 (2009)

    Article  ADS  CAS  Google Scholar 

  24. Han, J. et al. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genet. 4, e1000074 (2008)

    Article  Google Scholar 

  25. Stokowski, R. P. et al. A genomewide association study of skin pigmentation in a South Asian population. Am. J. Hum. Genet. 81, 1119–1132 (2007)

    Article  CAS  Google Scholar 

  26. Devlin, B. & Roeder, K. Genomic control for association studies. Biometrics 55, 997–1004 (1999)

    Article  CAS  Google Scholar 

  27. Rosenberg, N. A. & Nordborg, M. A general population-genetic model for the production by population structure of spurious genotype-phenotype associations in discrete, admixed, or spatially distributed populations. Genetics 173, 1665–1678 (2006)

    Article  CAS  Google Scholar 

  28. Nordborg, M. & Weigel, D. Next-generation genetics in plants. Nature 456, 720–723 (2008)

    Article  ADS  CAS  Google Scholar 

Download references


We thank B. Carvalho for his advice on how to modify the OLIGO package. This work was primarily supported by US National Science Foundation (NSF) grant DEB-0519961 (J.B., M.N.), US National Institutes of Health (NIH) grant GM073822 (J.O.B.), and NSF grant DEB-0723935 (M.N.). Additional support was provided by the Dropkin Foundation, NIH grant GM057994 and NSF grant MCB-0603515 (J.B.), the Max Planck Society (D.W., M.T.), the Austrian Academy of Sciences (M.N.), the University of Lille 1 (F.R.), NIH grant GM078536 and NIH grant P42ES007373 (D.E.S.), NIH grant GM62932 (J.C., D.W.), the Howard Hughes Medical Institute (J.C.), the Deutsche Forschungsgemeinschaft (DFG) SFB 680 (J.d.M.), a Marie Curie International Outgoing Fellowship ‘ANAVACO’ (project number 220833; G.W.), and a Gottfried Wilhelm Leibniz Award of the DFG (D.W.). The project would not have been possible without the existence of The Arabidopsis Information Resource (

Author information

Authors and Affiliations



J.O.B., J.B. and M.N. are equal senior authors. J.R.E. and D.W. generated the SNPs used in this project. S.A., M.H., Y.L., N.W.M., X.Z., J.O.B. and J.B. were responsible for the experimental aspects of genotyping. Y.S.H., B.J.V., M.H., T.T.H., R.J., X.Z., M.A.A., P.M., J.O.B., J.B. and M.N. were responsible for data management and the bioinformatics pipeline. S.A., I.B., B.B., J.C., C.D., M.D., J.d.M., N.F., J.M.K., J.D.G.J., T.M., A.N., F.R., D.E.S., C.T., M.T., M.B.T., D.W., J.B. and M.N. were responsible for phenotyping. S.A., Y.S.H., B.J.V., G.W., D.M., A.P., A.M.T., P.M. and M.N carried out the GWA analyses. Y.S.H. and D.M. developed the project website. M.N. wrote the paper with significant contributions from S.A., Y.S.H., B.J.V., G.W., A.P. and J.B. J.O.B., J.B. and M.N. designed and supervised the project.

Corresponding author

Correspondence to Magnus Nordborg.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Information which comprises: 1 Genotyping; 2 Association Mapping Methods; 3 Enrichment for a priori candidates, Supplementary Figures 1-152 with legends, Supplementary References and Supplementary Tables 1-7. (PDF 35247 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Atwell, S., Huang, Y., Vilhjálmsson, B. et al. Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines. Nature 465, 627–631 (2010).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing