The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Conditions Under Which Genome-Wide Association Studies Will be Positively Misleading
Open accessAbstract
Genome-wide association mapping is a popular method for using natural variation within a species to generate a genotype–phenotype map. Statistical association between an allele at a locus and the trait in question is used as evidence that variation at the locus is responsible for variation of the trait. Indirect association, however, can give rise to statistically significant results at loci unrelated to the trait. We use a haploid, three-locus, binary genetic model to describe the conditions under which these indirect associations become stronger than any of the causative associations in the organism—even to the point of representing the only associations present in the data. These indirect associations are the result of disequilibrium between multiple factors affecting a single trait. Epistasis and population structure can exacerbate the problem but are not required to create it. From a statistical point of view, indirect associations are true associations rather than the result of stochastic noise: they will not be ameliorated by increasing sampling size or marker density and can be reproduced in independent studies.
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Citations
Cites
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
Genomic Control for Association Studies
Devlin, B., & Roeder, K. (1999) · Biometrics · doi:10.1111/j.0006-341x.1999.00997.x · Cited by 3,162 · cited 2×
“…recognized that population structure can cause these kinds of spurious, nonrandom associations (Li 1969; Lander and Schork 1994), and considerable effort has been devoted to addressing this problem statistically (Devlin and Roeder 1999; Pritchard et al. 2000; Price et al. 2006; Yu et al. 2006).”
BackgroundVariance component model to account for sample structure in genome-wide association studies
Kang, H. M., Sul, J. H., Service, S. K., Zaitlen, N. A., Kong, S.-Y., Freimer, N. B., Sabatti, C., & Eskin, E. (2010) · Nature Genetics · doi:10.1038/ng.548 · Cited by 2,817
Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines
Atwell, S., Huang, Y. S., Vilhjálmsson, B. J., Willems, G., Horton, M., Li, Y., Meng, D., Platt, A., Tarone, A. M., Hu, T. T., et al. (2010) · Nature · doi:10.1038/nature08800 · Cited by 1,780
Self-citationGenes mirror geography within Europe
Novembre, J., Johnson, T., Bryc, K., Kutalik, Z., Boyko, A. R., Auton, A., Indap, A., King, K. S., Bergmann, S., Nelson, M. R., et al. (2008) · Nature · doi:10.1038/nature07331 · Cited by 1,479
Rare Variants Create Synthetic Genome-Wide Associations
Dickson, S. P., Wang, K., Krantz, I., Hakonarson, H., & Goldstein, D. B. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000294 · Cited by 857
Martínez, O., & Curnow, R. N. (1992) · Theoretical and Applied Genetics · doi:10.1007/bf00222330 · Cited by 355
Cited by
Turner, T. L., Stewart, A. D., Fields, A. T., Rice, W. R., & Tarone, A. M. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001336 · Cited by 297
Metadata
- Authors
- Platt, A., Vilhjálmsson, B. J., & Nordborg, M.
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-11-01
- Volume
- 186
- Issue
- 3
- Pages
- 1045-1052
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- OpenAlex
- W2120465937
- Cited by
- 197
- References
- 7
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- green
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