A simple and fast two‐locus quality control test to detect false positives due to batch effects in genome‐wide association studies
Open accessAbstract
The impact of erroneous genotypes having passed standard quality control (QC) can be severe in genome‐wide association studies, genotype imputation, and estimation of heritability and prediction of genetic risk based on single nucleotide polymorphisms (SNP). To detect such genotyping errors, a simple two‐locus QC method, based on the difference in test statistic of association between single SNPs and pairs of SNPs, was developed and applied. The proposed approach could detect many problematic SNPs with statistical significance even when standard single SNP QC analyses fail to detect them in real data. Depending on the data set used, the number of erroneous SNPs that were not filtered out by standard single SNP QC but detected by the proposed approach varied from a few hundred to thousands. Using simulated data, it was shown that the proposed method was powerful and performed better than other tested existing methods. The power of the proposed approach to detect erroneous genotypes was ∼80% for a 3% error rate per SNP. This novel QC approach is easy to implement and computationally efficient, and can lead to a better quality of genotypes for subsequent genotype‐phenotype investigations. Genet. Epidemiol. 34:854–862, 2010. © 2010 Wiley‐Liss, Inc.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
996 ASD cases and 1,287 controls of European ancestry were analysed to minimize confounds due to population differences.
“Ultimately, we analysed 996 ASD cases (876 trios) and 1,287 controls of European ancestry to minimize confounds due to population differences (Supplementary Figs 1 and 2 and Supplementary Table 1) 16 .”
From Functional impact of global rare copy number variation in autism spectrum disorders (2010) · cites this paper as [16]
The Methods > Real Data section describes endometriosis and WTCCC datasets, not an ASD cohort. Searches for the stated case and control counts, trios, ASD, and European ancestry found no passage in our copy that addresses the claimed sample or its selection to minimize population differences; page numbers were unavailable. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442 · see citing works
Finding the missing heritability of complex diseases
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., et al. (2009) · Nature · doi:10.1038/nature08494 · Cited by 8,336 · see citing works
Self-citationGenerating samples under a Wright–Fisher neutral model of genetic variation
Hudson, R. R. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.2.337 · Cited by 2,397 · see citing works
How to Interpret a Genome-wide Association Study
Pearson, T. A. (2008) · JAMA · doi:10.1001/jama.299.11.1335 · Cited by 964 · see citing works
Prediction of individual genetic risk to disease from genome-wide association studiesPreprint
Wray, N. R., Goddard, M. E., & Visscher, P. M. (2007) · Genome Research · doi:10.1101/gr.6665407 · Cited by 714 · see citing works
Self-citationVisscher, P. M., Medland, S. E., Ferreira, M. A. R., Morley, K. I., Zhu, G., Cornes, B. K., Montgomery, G. W., & Martin, N. G. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020041 · Cited by 613 · see citing works
Self-citationSizing up human height variation
Visscher, P. M. (2008) · Nature Genetics · doi:10.1038/ng0508-489 · Cited by 461 · see citing works
Self-citationSimultaneous Analysis of All SNPs in Genome-Wide and Re-Sequencing Association Studies
Hoggart, C. J., Whittaker, J. C., De Iorio, M., & Balding, D. J. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000130 · Cited by 321 · see citing works
Treloar, S. A., Wicks, J., Nyholt, D. R., Montgomery, G. W., Bahlo, M., Smith, V. E., Dawson, G., Mackay, I., Weeks, D. E., Bennett, S. T., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/432960 · Cited by 195 · see citing works
Self-citationPredicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data
Lee, S., van der Werf, J. H. J., Hayes, B. J., Goddard, M. E., & Visscher, P. M. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000231 · Cited by 194 · see citing works
Self-citationMitchell, A. A., Cutler, D. J., & Chakravarti, A. (2003) · The American Journal of Human Genetics · doi:10.1086/368203 · Cited by 169 · see citing works
WHAP: haplotype-based association analysis
Purcell, S., Daly, M. J., & Sham, P. C. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl580 · Cited by 154 · see citing works
Medland, S., Zayats, T., Glaser, B., Nyholt, D., Gordon, S., Wright, M., Montgomery, G., Campbell, M., Henders, A., Timpson, N., et al. (2010) · American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.02.017 · Cited by 95 · see citing works
Self-citationThe international endogene study: a collection of families for genetic research in endometriosis
Treloar, S. A., Hadfield, R. M., Montgomery, G. W., Lambert, A. W., Wicks, J., Barlow, D. H., O’Connor, D. T., & Kennedy, S. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(02)03341-1 · Cited by 90 · see citing works
Self-citationFerreira, M. A. R., Mangino, M., Brumme, C. J., Zhao, Z., Medland, S. E., Wright, M. J., Nyholt, D. R., Gordon, S. D., Campbell, M., McEvoy, B. P., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.12.008 · Cited by 88 · see citing works
Self-citationZaykin, D. V., Meng, Z., & Ehm, M. G. (2006) · The American Journal of Human Genetics · doi:10.1086/503710 · Cited by 85 · see citing works
Identification of probable genotyping errors by consideration of haplotypes
Becker, T., Valentonyte, R., Croucher, P. J. P., Strauch, K., Schreiber, S., Hampe, J., & Knapp, M. (2006) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201565 · Cited by 18 · see citing works
Missing call bias in high-throughput genotyping
Fu, W., Wang, Y., Wang, Y., et al. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-106 · Cited by 17 · see citing works
Marquard, V., Beckmann, L., Heid, I. M., et al. (2009) · BMC Genetics · doi:10.1186/1471-2156-10-3 · Cited by 16 · see citing works
Liu, W., Zhao, W., & Chase, G. A. (2006) · Human Heredity · doi:10.1159/000092141 · Cited by 14 · see citing works
Fardo, D. W., Ionita‐Laza, I., & Lange, C. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000572 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Functional impact of global rare copy number variation in autism spectrum disorders
Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., Regan, R., Conroy, J., Magalhaes, T. R., Correia, C., Abrahams, B. S., et al. (2010) · Nature · doi:10.1038/nature09146 · Cited by 2,013 · see citing works
Estimating Missing Heritability for Disease from Genome-wide Association Studies
Lee, S. H., Wray, N. R., Goddard, M. E., & Visscher, P. M. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.02.002 · Cited by 1,064 · see citing works
Self-citationIdentification of common variants influencing risk of the tauopathy progressive supranuclear palsy
PSP Genetics Study Group, Höglinger, G. U., Melhem, N. M., Dickson, D. W., Sleiman, P. M. A., Wang, L.-S., Klei, L., Rademakers, R., de Silva, R., Litvan, I., et al. (2011) · Nature Genetics · doi:10.1038/ng.859 · Cited by 603 · see citing works
Lee, S. H., Harold, D., Nyholt, D. R., ANZGene Consortium, International Endogene Consortium, the Genetic and Environmental Risk for Alzheimer's disease (GERAD1) Consortium, Goddard, M. E., Zondervan, K. T., Williams, J., Montgomery, G. W., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/dds491 · Cited by 217 · see citing works
Self-citationGenome-wide association identifies the first risk loci for psychosis in Alzheimer disease
DeMichele-Sweet, M. A. A., Klei, L., Creese, B., Harwood, J. C., Weamer, E. A., McClain, L., Sims, R., Hernandez, I., Moreno-Grau, S., Tárraga, L., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01152-8 · Cited by 64 · see citing works
The Autism Genome Project, Anney, R. J. L., Kenny, E. M., O'Dushlaine, C., Yaspan, B. L., Parkhomenka, E., Buxbaum, J. D., Sutcliffe, J., Gill, M., Gallagher, L., et al. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2011.75 · Cited by 43 · see citing works
- Authors
- Lee, S. H., Nyholt, D. R., Macgregor, S., Henders, A. K., Zondervan, K. T., Montgomery, G. W., & Visscher, P. M.
- Affiliations
- QIMR Berghofer Medical Research Institute (AU)
- John Radcliffe Hospital (GB)
- Corresponding author
- Lee, Sang Hong
- ORCID
- Venue
- Genetic Epidemiology
- Publisher
- Wiley
- Published
- 2010-11-22
- Volume
- 34
- Issue
- 8
- Pages
- 854-862
- ISSN
- 0741-0395 (ISSN-L)
- 1098-2272
- PMC
- PMC3674525
- OpenAlex
- W2156676902
- Cited by
- 33
- References
- 22
- Citations by year
- 2021: 1 · 2020: 2 · 2019: 3 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 7
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genetic Epidemiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion)
- Faculty of Health; Institute of Health and Biomedical Innovation
- Funders
- Wellcome Trust (085235, 084766, 076113)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- genotype quality control, batch effects, false positives, genotyping errors, single nucleotide polymorphisms, genome-wide association study, statistical power
- MeSH terms
- Genotype, Humans, Models, Genetic, Quality Control, Genome, Human, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Loci
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
