Association mapping: critical considerations shift from genotyping to experimental design
Open accessAbstract
The goal of many plant scientists' research is to explain natural phenotypic variation in terms of simple changes in DNA sequence. Traditionally, linkage mapping has been the most commonly employed method to reach this goal: experimental crosses are made to generate a family with known relatedness, and attempts are made to identify cosegregation of genetic markers and phenotypes within this family. In vertebrate systems, association mapping (also known as linkage disequilibrium mapping) is increasingly being adopted as the mapping method of choice. Association mapping involves searching for genotype-phenotype correlations in unrelated individuals and often is more rapid and cost-effective than traditional linkage mapping. We emphasize here that linkage and association mapping are complementary approaches and are more similar than is often assumed. Unlike in vertebrates, where controlled crosses can be expensive or impossible (e.g., in humans), the plant scientific community can exploit the advantages of both controlled crosses and association mapping to increase statistical power and mapping resolution. While the time and money required for the collection of genotype data were critical considerations in the past, the increasing availability of inexpensive DNA sequencing and genotyping methods should prompt researchers to shift their attention to experimental design. This review provides thoughts on finding the optimal experimental mix of association mapping using unrelated individuals and controlled crosses to identify the genes underlying phenotypic variation.
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Association mapping is a powerful approach for identifying genotype-phenotype correlations within a diverse collection of germplasms or breeding materials.
“Association mapping (also known as linkage disequilibrium mapping) is a powerful approach for identifying genotype (marker)-phenotype (trait) correlations within a diverse collection of germplasms or breeding materials (Myles et al., 2009; Wang M. L. et al., 2011).”
From Development and identification of SSR markers associated with starch properties and β-carotene content in the storage root of sweet potato (Ipomoea batatas L.) (2016) · cites this paper as Myles et al., 2009
Association analyses were performed using various mixed models with subpopulation membership percentages as fixed covariates or kinship as a random effect, including naive, Q, Q+K, and K models.
“We performed association analyses using various mixed models (Yu et al., 2006; Myles et al., 2009), which with subpopulation membership percentages as fixed covariates or kinship as a random effect, including (1) naive model, without controlling for Q and K, (2) Q model, controlling for Q, (3) Q+K model, controlling for both Q and K, and (4) K model, controlling for K (Supplementary Material 6).”
From Development and identification of SSR markers associated with starch properties and β-carotene content in the storage root of sweet potato (Ipomoea batatas L.) (2016) · cites this paper as Myles et al., 2009
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Cites
Inference of Population Structure Using Multilocus Genotype Data
Pritchard, J. K., Stephens, M., & Donnelly, P. (2000) · Genetics · doi:10.1093/genetics/155.2.945 · Cited by 33,871 · see citing works
genalex 6: genetic analysis in Excel. Population genetic software for teaching and research
Peakall, R., & Smouse, P. E. (2005) · Molecular Ecology Notes · doi:10.1111/j.1471-8286.2005.01155.x · Cited by 16,596 · see citing works
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248 · see citing works
Prediction of Total Genetic Value Using Genome-Wide Dense Marker Maps
Meuwissen, T. H. E., Hayes, B. J., & Goddard, M. E. (2001) · Genetics · doi:10.1093/genetics/157.4.1819 · Cited by 7,917 · see citing works
Efficient Methods to Compute Genomic Predictions
VanRaden, P. M. (2008) · Journal of Dairy Science · doi:10.3168/jds.2007-0980 · Cited by 6,050 · see citing works
The Future of Genetic Studies of Complex Human Diseases
Risch, N., & Merikangas, K. (1996) · Science · doi:10.1126/science.273.5281.1516 · Cited by 5,355 · see citing works
Yu, J., Pressoir, G., Briggs, W. H., Bi, I. V., Yamasaki, M., Doebley, J., McMullen, M. D., Gaut, B. S., Nielsen, D. M., Holland, J. B., et al. (2005) · Nature Genetics · doi:10.1038/ng1702 · Cited by 4,155 · see citing works
Self-citationSpielman, R. S., McGinnis, R. E., & Ewens, W. J. (1993) · PubMed · Cited by 3,679 · see citing works
Genetic Dissection of Complex Traits
Lander, E. S., & Schork, N. J. (1994) · Science · doi:10.1126/science.8091226 · Cited by 3,425 · see citing works
Best Linear Unbiased Estimation and Prediction under a Selection Model
Henderson, C. (1975) · Biometrics · doi:10.2307/2529430 · Cited by 2,513 · see citing works
Association mapping in structured populations.
Pritchard, J. K., Stephens, M., Rosenberg, N., & Donnelly, P. (2000) · American Journal of Human Genetics · doi:10.1086/302959 · Cited by 2,066 · see citing works
Efficient Control of Population Structure in Model Organism Association Mapping
Kang, H. M., Zaitlen, N., Wade, C. M., Kirby, A. W., Heckerman, D. E., Daly, M. J., & Eskin, E. (2008) · Genetics · doi:10.1534/genetics.107.080101 · Cited by 1,848 · see citing works
Personal genomes: The case of the missing heritability
Maher, B. (2008) · Nature · doi:10.1038/456018a · Cited by 1,737 · see citing works
Structure of Linkage Disequilibrium in Plants
Flint-Garcia, S. A., Thornsberry, J. M., & Buckler, E. S. (2003) · Annual Review of Plant Biology · doi:10.1146/annurev.arplant.54.031902.134907 · Cited by 1,700 · see citing works
Self-citationGenomic Selection for Crop Improvement
Heffner, E. L., Sorrells, M. E., & Jannink, J. (2009) · Crop Science · doi:10.2135/cropsci2008.08.0512 · Cited by 1,661 · see citing works
The Genetic Architecture of Maize Flowering Time
Buckler, E. S., Holland, J. B., Bradbury, P. J., Acharya, C. B., Brown, P. J., Browne, C., Ersoz, E. S., Flint-Garcia, S. A., Garcia, A. R., Glaubitz, J. C., et al. (2009) · Science · doi:10.1126/science.1174276 · Cited by 1,462 · see citing works
Self-citationGenetic Mapping in Human Disease
Altshuler, D., Daly, M. J., & Lander, E. S. (2008) · Science · doi:10.1126/science.1156409 · Cited by 1,452 · see citing works
Status and Prospects of Association Mapping in Plants
Zhu, C., Gore, M. A., Buckler, E. S., & Yu, J. (2008) · The Plant Genome · doi:10.3835/plantgenome2008.02.0089 · Cited by 1,344 · see citing works
Self-citationStructure of linkage disequilibrium and phenotypic associations in the maize genome
Remington, D. L., Thornsberry, J. M., Matsuoka, Y., Wilson, L. M., Whitt, S. R., Doebley, J., Kresovich, S., Goodman, M. M., & Buckler, E. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201394398 · Cited by 1,258 · see citing works
Self-citationThe New Genomics: Global Views of Biology
Lander, E. S. (1996) · Science · doi:10.1126/science.274.5287.536 · Cited by 1,174 · see citing works
Genetic Structure and Diversity in Oryza sativa L.
Garris, A. J., Tai, T. H., Coburn, J., Kresovich, S., & McCouch, S. (2005) · Genetics · doi:10.1534/genetics.104.035642 · Cited by 1,137 · see citing works
The Collaborative Cross, a community resource for the genetic analysis of complex traits
Churchill, G. A., Bogue, M. A., Paigen, B. J., Paigen, K., Pan, H.-J., Svenson, K. L., Airey, D. C., Allayee, H., Angel, J. M., Attie, A., et al. (2004) · Nature Genetics · doi:10.1038/ng1104-1133 · Cited by 1,114 · see citing works
Self-citationDwarf8 polymorphisms associate with variation in flowering time
Thornsberry, J. M., Goodman, M. M., Doebley, J., Kresovich, S., Nielsen, D. M., & Buckler, E. S. (2001) · Nature Genetics · doi:10.1038/90135 · Cited by 1,102 · see citing works
Self-citationMapping genes for complex traits in domestic animals and their use in breeding programmes
Goddard, M. E., & Hayes, B. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2575 · Cited by 1,100 · see citing works
Genetic Design and Statistical Power of Nested Association Mapping in Maize
Yu, J., Holland, J. B., McMullen, M. D., & Buckler, E. S. (2008) · Genetics · doi:10.1534/genetics.107.074245 · Cited by 1,082 · see citing works
Self-citationApplications of single nucleotide polymorphisms in crop genetics
Rafalski, A. J. (2002) · Current Opinion in Plant Biology · doi:10.1016/s1369-5266(02)00240-6 · Cited by 1,069 · see citing works
Association Mapping of Kernel Size and Milling Quality in Wheat (Triticum aestivum L.) Cultivars
Breseghello, F., & Sorrells, M. E. (2005) · Genetics · doi:10.1534/genetics.105.044586 · Cited by 1,026 · see citing works
The Pattern of Polymorphism in Arabidopsis thaliana
Nordborg, M., Hu, T. T., Ishino, Y., Jhaveri, J., Toomajian, C., Zheng, H., Bakker, E. G., Calabrese, P. P., Gladstone, J., Goyal, R., et al. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030196 · Cited by 969 · see citing works
Maize association population: a high‐resolution platform for quantitative trait locus dissection
Flint-Garcia, S. A., Thuillet, A., Yu, J., Pressoir, G., Romero, S. M., Mitchell, S. E., Doebley, J., Kresovich, S., Goodman, M. M., & Buckler, E. S. (2005) · The Plant Journal · doi:10.1111/j.1365-313x.2005.02591.x · Cited by 916 · see citing works
Self-citationStrategy for applying genome‐wide selection in dairy cattle
Schaeffer, L. R. (2006) · Journal of Animal Breeding and Genetics · doi:10.1111/j.1439-0388.2006.00595.x · Cited by 863 · see citing works
Natural Genetic Variation in Lycopene Epsilon Cyclase Tapped for Maize Biofortification
Harjes, C., Rocheford, T., Bai, L., Brutnell, T. P., Kandianis, C. B., Sowinski, S. G., Stapleton, A. E., Vallabhaneni, R., Williams, M., Wurtzel, E. T., et al. (2008) · Science · doi:10.1126/science.1150255 · Cited by 787 · see citing works
Self-citationAn Arabidopsis Example of Association Mapping in Structured Samples
Zhao, K., Aranzana, M. J., Kim, S. H., Lister, C., Shindo, C., Tang, C., Toomajian, C., Zheng, H., Dean, C., Marjoram, P., et al. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0030004 · Cited by 742 · see citing works
Patterns of DNA sequence polymorphism along chromosome 1 of maize ( Zea mays ssp. mays L.)
Tenaillon, M. I., Sawkins, M. C., Long, A. D., Gaut, R. L., Doebley, J., & Gaut, B. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151244298 · Cited by 701 · see citing works
Recombination and linkage disequilibrium in Arabidopsis thaliana
Kim, S., Plagnol, V., Hu, T. T., Toomajian, C., Clark, R. M., Ossowski, S., Ecker, J. R., Weigel, D., & Nordborg, M. (2007) · Nature Genetics · doi:10.1038/ng2115 · Cited by 547 · see citing works
Genetic architecture of complex traits in plants
Holland, J. B. (2007) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2007.01.003 · Cited by 526 · see citing works
Ascertainment bias in studies of human genome-wide polymorphismPreprint
Clark, A. G., Hubisz, M. J., Bustamante, C. D., Williamson, S., & Nielsen, R. (2005) · Genome Research · doi:10.1101/gr.4107905 · Cited by 503 · see citing works
Next-generation genetics in plants
Nordborg, M., & Weigel, D. (2008) · Nature · doi:10.1038/nature07629 · Cited by 453 · see citing works
A phenylalanine in DGAT is a key determinant of oil content and composition in maize
Zheng, P., Allen, W. B., Roesler, K. R., Williams, M. E., Zhang, S., Li, J., Glassman, K., Ranch, J., Nubel, D., Solawetz, W., et al. (2008) · Nature Genetics · doi:10.1038/ng.85 · Cited by 449 · see citing works
Aranzana, M. J., Kim, S., Zhao, K., Bakker, E. G., Horton, M., Jakob, K., Lister, C., Molitor, J., Shindo, C., Tang, C., et al. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010060 · Cited by 448 · see citing works
Nordborg, M. (2000) · Genetics · doi:10.1093/genetics/154.2.923 · Cited by 430 · see citing works
Blott, S. C., Kim, J.-J., Moisio, S., Schmidt‐Küntzel, A., Cornet, A. M., Berzi, P., Cambisano, N., Ford, C. A., Grisart, B., Johnson, D., et al. (2003) · Genetics · doi:10.1093/genetics/163.1.253 · Cited by 417 · see citing works
Genetic architecture of quantitative traits in mice, flies, and humansPreprint
Jonathan Flint, C., & Mackay, T. F. C. (2009) · Genome Research · doi:10.1101/gr.086660.108 · Cited by 404 · see citing works
Lin, Y., Schertz, K. F., & Paterson, A. H. (1995) · Genetics · doi:10.1093/genetics/141.1.391 · Cited by 399 · see citing works
Progress and challenges in genome-wide association studies in humans
Donnelly, P. (2008) · Nature · doi:10.1038/nature07631 · Cited by 358 · see citing works
Dissection of Maize Kernel Composition and Starch Production by Candidate Gene Association
Wilson, L. M., Whitt, S. R., Ibáñez, A., et al. (2004) · The Plant Cell · doi:10.1105/tpc.104.025700 · Cited by 345 · see citing works
Genetic diversity and selection in the maize starch pathway
Whitt, S. R., Wilson, L. M., Tenaillon, M. I., Gaut, B. S., & Buckler, E. S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202476999 · Cited by 339 · see citing works
Self-citationLaurie, C. C., Chasalow, S. D., LeDeaux, J. R., McCarroll, R. M., Bush, D., Hauge, B. M., Lai, C., Clark, D., Rocheford, T., & Dudley, J. W. (2004) · Genetics · doi:10.1534/genetics.104.029686 · Cited by 309 · see citing works
Meuwissen, T. H. E., Karlsen, A., Lien, S., Olsaker, I., & Goddard, M. E. (2002) · Genetics · doi:10.1093/genetics/161.1.373 · Cited by 283 · see citing works
Lijavetzky, D., Cabezas, J. A., Ibáñez, A., Rodríguez, V., & Martínez-Zapater, J. M. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-424 · Cited by 272 · see citing works
Camus‐Kulandaivelu, L., Veyrieras, J., Madur, D., Combes, V., Fourmann, M., Barraud, S., Dubreuil, P., Gouesnard, B., Manicacci, D., & Charcosset, A. (2006) · Genetics · doi:10.1534/genetics.105.048603 · Cited by 258 · see citing works
Comparison of Mixed-Model Approaches for Association Mapping
Stich, B., Möhring, J., Piepho, H., Heckenberger, M., Buckler, E. S., & Melchinger, A. E. (2008) · Genetics · doi:10.1534/genetics.107.079707 · Cited by 257 · see citing works
Self-citationHeuertz, M., Paoli, E. D., Källman, T., Larsson, H., Jurman, I., Morgante, M., Lascoux, M., & Gyllenstrand, N. (2006) · Genetics · doi:10.1534/genetics.106.065102 · Cited by 253 · see citing works
Malosetti, M., van der Linden, C. G., Vosman, B., & van Eeuwijk, F. A. (2006) · Genetics · doi:10.1534/genetics.105.054932 · Cited by 232 · see citing works
Balasubramanian, S., Sureshkumar, S., Agrawal, M., Michael, T. P., Wessinger, C., Maloof, J., Clark, R. M., Warthmann, N., Chory, J., & Weigel, D. (2006) · Nature Genetics · doi:10.1038/ng1818 · Cited by 216 · see citing works
Griffiths, H. (1993) · Springer eBooks · doi:10.1007/978-94-011-1566-7_11 · Cited by 173 · see citing works
Genetic analysis of complex disease.
Scott, W. K., Pericak-Vance, M. A., & Haines, J. L. (1997) · PubMed · Cited by 163 · see citing works
FRIGIDA-Independent Variation in Flowering Time of Natural Arabidopsis thaliana Accessions
Werner, J. D., Borevitz, J., Uhlenhaut, N. H., Ecker, J. R., Chory, J., & Weigel, D. (2005) · Genetics · doi:10.1534/genetics.104.036533 · Cited by 156 · see citing works
Andersen, J. R., Schrag, T. A., Melchinger, A. E., et al. (2005) · Theoretical and Applied Genetics · doi:10.1007/s00122-005-1996-6 · Cited by 146 · see citing works
Association genetics in Pinus taeda L. II. Carbon isotope discrimination
González‐Martínez, S. C., Huber, D., Ersoz, E. S., Davis, J. M., & Neale, D. B. (2008) · Heredity · doi:10.1038/hdy.2008.21 · Cited by 137 · see citing works
Self-citationEstimation of coefficient of coancestry using molecular markers in maize
Bernardo, R. (1993) · Theoretical and Applied Genetics · doi:10.1007/bf00215047 · Cited by 99 · see citing works
Genetic Analysis of Complex Diseases
Scott, W. K., Pericak‐Vance, M. A., & Haines, J. L. (1997) · Science · doi:10.1126/science.275.5304.1327 · Cited by 97 · see citing works
Using mating designs to uncover QTL and the genetic architecture of complex traits
Verhoeven, K. J. F., Jannink, J., & McIntyre, L. M. (2005) · Heredity · doi:10.1038/sj.hdy.6800763 · Cited by 96 · see citing works
Joint Linkage and Linkage Disequilibrium Mapping of Quantitative Trait Loci in Natural Populations
Wu, R., Ma, C., & Casella, G. (2002) · Genetics · doi:10.1093/genetics/160.2.779 · Cited by 87 · see citing works
Joint Linkage and Linkage Disequilibrium Mapping in Natural Populations
Wu, R., & Zeng, Z. (2001) · Genetics · doi:10.1093/genetics/157.2.899 · Cited by 84 · see citing works
Jung, M., Ching, A., Bhattramakki, D., et al. (2004) · Theoretical and Applied Genetics · doi:10.1007/s00122-004-1695-8 · Cited by 83 · see citing works
Mouse Genome-Wide Association Mapping Needs Linkage Analysis to Avoid False-Positive Loci
Manenti, G., Galvan, A., Pettinicchio, A., Trincucci, G., Spada, E., Zolin, A., Milani, S., González‐Neira, A., & Dragani, T. A. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000331 · Cited by 67 · see citing works
Marker-based estimates of identity by descent and alikeness in state among maize inbreds
Bernardo, R., Murigneux, A., & Karaman, Z. (1996) · Theoretical and Applied Genetics · doi:10.1007/bf00225755 · Cited by 30 · see citing works
An Arabidopsis Example of Association Mapping in Structured Samples
Zhao, K., Aranzana, M. J., Kim, S. H., et al. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0030004.eor · Cited by 26 · see citing works
Marker-based estimates of identity by descent and alikeness in state among maize inbreds
Bernardo, R., Murigneux, A., & Karaman, Z. (1996) · Theoretical and Applied Genetics · doi:10.1007/s001220050275 · Cited by 7 · see citing works
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Genotyping‐by‐Sequencing for Plant Breeding and Genetics
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- Authors
- Myles, S., Peiffer, J., Brown, P. J., Ersoz, E. S., Zhang, Z., Costich, D. E., & Buckler, E. S.
- Affiliations
- Cornell University (US)
- Agricultural Research Service (US)
- Venue
- The Plant Cell
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-08
- Volume
- 21
- Issue
- 8
- Pages
- 2194-2202
- ISSN
- 1040-4651 (ISSN-L)
- 1532-298X
- PMC
- PMC2751942
- OpenAlex
- W2100082928
- Cited by
- 857
- References
- 69
- Citations by year
- 2026: 25 · 2025: 31 · 2024: 45 · 2023: 36 · 2022: 53 · 2021: 56 · 2020: 53 · 2019: 52 · 2018: 50 · 2017: 68 · 2016: 62 · 2015: 66 · 2014: 54 · 2013: 63 · 2012: 58
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Plant Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- association mapping, linkage mapping, linkage disequilibrium, experimental design, plant genetics, genotype-phenotype correlation, statistical power, mapping resolution, genotyping, controlled crosses
- MeSH terms
- Animals, Chromosome Mapping, Genotype, Humans, Phenotype, Research Design
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