Estimation of significance thresholds for genomewide association scans
Open accessAbstract
The question of what significance threshold is appropriate for genomewide association studies is somewhat unresolved. Previous theoretical suggestions have yet to be validated in practice, whereas permutation testing does not resolve a discrepancy between the genomewide multiplicity of the experiment and the subset of markers actually tested. We used genotypes from the Wellcome Trust Case‐Control Consortium to estimate a genomewide significance threshold for the UK Caucasian population. We subsampled the genotypes at increasing densities, using permutation to estimate the nominal P‐value for 5% family‐wise error. By extrapolating to infinite density, we estimated the genomewide significance threshold to be about 7.2 × 10−8. To reduce the computation time, we considered Patterson's eigenvalue estimator of the effective number of tests, but found it to be an order of magnitude too low for multiplicity correction. However, by fitting a Beta distribution to the minimum P‐value from permutation replicates, we showed that the effective number is a useful heuristic and suggest that its estimation in this context is an open problem. We conclude that permutation is still needed to obtain genomewide significance thresholds, but with subsampling, extrapolation and estimation of an effective number of tests, the threshold can be standardized for all studies of the same population. Genet. Epidemiol. 2008. © 2008 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?
The best P-value for the chromosome 17 haplotype is genome-wide significant at the empirical threshold for European populations and was supported by association of multiple variants in the region.
“This P-value is genome-wide significant at the empirical threshold for European populations29 and was well supported by association of multiple variants in the region (Figure 1 and Supplementary Table 1).”
From Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease (2015) · cites this paper as [29]
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
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Why Most Published Research Findings Are False
Ioannidis, J. P. A. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020124 · Cited by 10,505 · 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
A haplotype map of the human genome
The International HapMap Consortium (2005) · Nature · doi:10.1038/nature04226 · Cited by 5,858 · 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
Population Structure and Eigenanalysis
Patterson, N., Price, A. L., & Reich, D. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020190 · Cited by 5,280 · see citing works
Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results
Lander, E. S., & Kruglyak, L. (1995) · Nature Genetics · doi:10.1038/ng1195-241 · Cited by 5,196 · see citing works
Empirical threshold values for quantitative trait mapping.
Churchill, G. A., & Doerge, R. W. (1994) · Genetics · doi:10.1093/genetics/138.3.963 · Cited by 4,950 · see citing works
Rectangular Confidence Regions for the Means of Multivariate Normal Distributions
Šidák, Z. (1967) · Journal of the American Statistical Association · doi:10.1080/01621459.1967.10482935 · Cited by 2,904 · see citing works
The Wellcome Trust Case Control Consortium, U.K.
Mossman, K. (2008) · Scientific American · doi:10.1038/scientificamerican0108-42a · Cited by 2,714 · see citing works
A new multipoint method for genome-wide association studies by imputation of genotypes
Marchini, J., Howie, B., Myers, S., McVean, G., & Donnelly, P. (2007) · Nature Genetics · doi:10.1038/ng2088 · Cited by 2,609 · see citing works
Multiple Comparison Procedures
Hochberg, Y., & Tamhane, A. C. (1987) · Wiley Series in Probability and Statistics · doi:10.1002/9780470316672 · Cited by 2,389 · see citing works
Resampling-Based Multiple Testing: Examples and Methods for p-Value Adjustment
Martín, M. A., Westfall, P. H., & Young, S. (1993) · Biometrics · doi:10.2307/2533464 · Cited by 2,308 · see citing works
Multiple Comparison Procedures
Hahs-Vaughn, D., & Lomax, R. (2013) · Routledge eBooks · doi:10.4324/9780203137819-17 · Cited by 2,132 · see citing works
Wacholder, S., Chanock, S. J., García‐Closas, M., ghormli, L. K. E., & Rothman, N. (2004) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djh075 · Cited by 1,743 · see citing works
Sequential tests for the detection of linkage.
Morton, N. E. (1955) · PubMed · Cited by 1,590 · see citing works
Rectangular Confidence Regions for the Means of Multivariate Normal Distributions
Šidák, Z. (1967) · Journal of the American Statistical Association · doi:10.2307/2283989 · Cited by 1,455 · see citing works
Empirical Bayes methods and false discovery rates for microarrays
Efron, B., & Tibshirani, R. (2002) · Genetic Epidemiology · doi:10.1002/gepi.1124 · Cited by 684 · see citing works
A Bayesian Measure of the Probability of False Discovery in Genetic Epidemiology Studies
Wakefield, J. (2007) · The American Journal of Human Genetics · doi:10.1086/519024 · Cited by 486 · see citing works
Why Most Published Research Findings Are False
Ioannidis, J. P. A. (2019) · CHANCE · doi:10.1080/09332480.2019.1579573 · Cited by 473 · see citing works
Evaluating coverage of genome-wide association studies
Barrett, J. C., & Cardon, L. R. (2006) · Nature Genetics · doi:10.1038/ng1801 · Cited by 415 · see citing works
Evaluating and improving power in whole-genome association studies using fixed marker sets
Pe’er, I., de Bakker, P. I. W., Maller, J., Yelensky, R., Altshuler, D., & Daly, M. J. (2006) · Nature Genetics · doi:10.1038/ng1816 · Cited by 275 · see citing works
Modeling Household Transmission of American Trypanosomiasis
Cohen, J. E., & Gürtler, R. E. (2001) · Science · doi:10.1126/science.1060638 · Cited by 255 · see citing works
Dudbridge, F., & Koeleman, B. P. C. (2004) · The American Journal of Human Genetics · doi:10.1086/423738 · Cited by 166 · see citing works
Self-citationBetting Odds and Genetic Associations
Thomas, D. C., & Clayton, D. G. (2004) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djh094 · Cited by 154 · see citing works
Rank truncated product of P‐values, with application to genomewide association scans
Dudbridge, F., & Koeleman, B. P. C. (2003) · Genetic Epidemiology · doi:10.1002/gepi.10264 · Cited by 122 · see citing works
Self-citationGenomics, Prior Probability, and Statistical Tests of Multiple HypothesesPreprint
Manly, K. F., Nettleton, D. S., & Hwang, J. T. G. (2004) · Genome Research · doi:10.1101/gr.2156804 · Cited by 86 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Variance 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 · see citing works
Benefits and limitations of genome-wide association studies
Tam, V., Patel, N. K., Turcotte, M., Bossé, Y., Paré, G., & Meyre, D. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0127-1 · Cited by 2,092 · see citing works
A Large-Scale, Consortium-Based Genomewide Association Study of Asthma
Moffatt, M. F., Gut, I. G., Démenais, F., Strachan, D. P., Bouzigon, E., Heath, S. C., von Mutius, E., Farrall, M., Lathrop, M. G., & Cookson, W. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0906312 · Cited by 2,003 · see citing works
Genome-wide association study identifies five new schizophrenia loci
The Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011) · Nature Genetics · doi:10.1038/ng.940 · Cited by 1,919 · see citing works
Self-citationLi, B., & Leal, S. M. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.06.024 · Cited by 1,527 · see citing works
Power and predictive accuracy of polygenic risk scores
Dudbridge, F. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003348 · Cited by 1,509 · see citing works
“Assuming this is equivalent to about one million independent common SNPs [32], the required sample sizes are shown in Figure 4 and Table 5.”
BackgroundSelf-citationGenome-wide meta-analyses identify multiple loci associated with smoking behavior
The Tobacco and Genetics Consortium (2010) · Nature Genetics · doi:10.1038/ng.571 · Cited by 1,098 · see citing works
Chapter 11: Genome-wide association studies
Bush, W. S., & Moore, J. H. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002822 · Cited by 1,171 · see citing works
Multiple common variants for celiac disease influencing immune gene expression
Dubois, P. C. A., Trynka, G., Franke, L., Hunt, K. A., Romanos, J., Curtotti, A., Zhernakova, A., Heap, G., Ádány, R., Aromaa, A. J., et al. (2010) · Nature Genetics · doi:10.1038/ng.543 · Cited by 1,026 · see citing works
Li, M.-X., Yeung, J. M. Y., Cherny, S. S., & Sham, P. C. (2012) · Human Genetics · doi:10.1007/s00439-011-1118-2 · Cited by 962 · see citing works
A Review of Feature Selection Methods for Machine Learning-Based Disease Risk Prediction
Pudjihartono, N., Fadason, T., Kempa-Liehr, A. W., & O'Sullivan, J. M. (2022) · Frontiers in Bioinformatics · doi:10.3389/fbinf.2022.927312 · Cited by 965 · see citing works
A tutorial on conducting genome‐wide association studies: Quality control and statistical analysis
Marees, A. T., de Kluiver, H., Stringer, S., Vorspan, F., Curis, E., Cynthia Marie-claire, A., & Derks, E. M. (2018) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.1608 · Cited by 820 · see citing works
Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study
Richards, J. B., Rivadeneira, F., Inouye, M., Pastinen, T., Soranzo, N., Wilson, S. G., Andrew, T., Falchi, M., Gwilliam, R., Ahmadi, K. R., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60599-1 · Cited by 680 · see citing works
Yano, K., Yamamoto, E., Aya, K., Takeuchi, H., Lo, P.-C., Hu, L. H., Yamasaki, M., Yoshida, S., Kitano, H., Hirano, K., et al. (2016) · Nature Genetics · doi:10.1038/ng.3596 · Cited by 678 · see citing works
Kolz, M., Johnson, T., Sanna, S., Teumer, A., Vitart, V., Perola, M., Mangino, M., Albrecht, E., Wallace, C., Farrall, M., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000504 · Cited by 659 · see citing works
23andMe Research Team, Walters, R. K., Polimanti, R., Johnson, E. C., McClintick, J. N., Adams, M. J., Adkins, A. E., Aliev, F., Bacanu, S.-A., Batzler, A., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0275-1 · Cited by 632 · see citing works
Meta-analysis methods for genome-wide association studies and beyond
Evangelou, E., & Ioannidis, J. P. A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3472 · Cited by 596 · see citing works
Statistical power and significance testing in large-scale genetic studies
Sham, P. C., & Purcell, S. M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3706 · Cited by 573 · see citing works
Practical aspects of imputation-driven meta-analysis of genome-wide association studies
de Bakker, P. I. W., Ferreira, M. A. R., Jia, X., Neale, B. M., Raychaudhuri, S., & Voight, B. F. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn288 · Cited by 531 · see citing works
Genetics of breast cancer: a topic in evolution
Shiovitz, S., & Korde, L. A. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv022 · Cited by 536 · see citing works
Basic statistical analysis in genetic case-control studies
Clarke, G. M., Anderson, C. A., Pettersson, F. H., Cardon, L. R., Morris, A. P., & Zondervan, K. T. (2011) · Nature Protocols · doi:10.1038/nprot.2010.182 · Cited by 507 · see citing works
New susceptibility locus for coronary artery disease on chromosome 3q22.3
Italian Atherosclerosis, T., Erdmann, J., Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Cardiogenics Consortium, Großhennig, A., Braund, P. S., König, I. R., Hengstenberg, C., Hall, A. S., et al. (2009) · Nature Genetics · doi:10.1038/ng.307 · Cited by 484 · see citing works
A genome-wide association study of alcohol dependence
Bierut, L. J., Agrawal, A., Bucholz, K. K., Doheny, K. F., Laurie, C., Pugh, E., Fisher, S., Fox, L., Howells, W., Bertelsen, S., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911109107 · Cited by 457 · see citing works
Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder
Neale, B. M., Medland, S. E., Ripke, S., Asherson, P., Franke, B., Lesch, K.-P., Faraone, S. V., Nguyen, T. T., Schäfer, H., Holmans, P., et al. (2010) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2010.06.008 · Cited by 450 · see citing works
Genomewide Association Studies: History, Rationale, and Prospects for Psychiatric Disorders
Psychiatric GWAS Consortium Coordinating Committee (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.08091354 · Cited by 450 · see citing works
The harmonic mean <i>p</i> -value for combining dependent tests
Wilson, D. J. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814092116 · Cited by 449 · see citing works
Six Persistent Research Misconceptions
Rothman, K. J. (2014) · Journal of General Internal Medicine · doi:10.1007/s11606-013-2755-z · Cited by 440 · see citing works
Genome-wide association studies in ADHD
Franke, B., Neale, B., & Faraone, S. (2009) · Human Genetics · doi:10.1007/s00439-009-0663-4 · Cited by 462 · see citing works
Yu, D., Sul, J. H., Tsetsos, F., Nawaz, M. S., Huang, A. Y., Zelaya, I., Illmann, C., Osiecki, L., Darrow, S. M., Hirschtritt, M. E., et al. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.18070857 · Cited by 410 · see citing works
Lasky-Su, J. A., Neale, B. M., Franke, B., Anney, R., Zhou, K., Maller, J., Vásquez, A. A., Chen, W., Asherson, P. J., Buitelaar, J. K., et al. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30867 · Cited by 388 · see citing works
Genome-wide association study of obsessive-compulsive disorder
Stewart, S. E., Yu, D., Scharf, J. M., Neale, B. M., Fagerness, J. A., Mathews, C. A., Arnold, P. D., Evans, P. D., Gamazon, E. R., Osiecki, L., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.85 · Cited by 384 · see citing works
Genome-wide Association Study of Alcohol Dependence
Treutlein, J., Cichon, S., Ridinger, M., Wodarz, N., Soyka, M., Zill, P., Maier, W., Moessner, R., Gäebel, W., Dahmen, N., et al. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.83 · Cited by 380 · see citing works
Genome-wide and fine-resolution association analysis of malaria in West Africa
Jallow, M., Teo, Y. Y., Small, K. S., Rockett, K. A., Deloukas, P., Clark, T. G., Kivinen, K., Bojang, K., Conway, D. J., Pinder, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.388 · Cited by 374 · see citing works
Meta-analysis of genome-wide association studies for personality
de Moor, M. H. M., Costa, P. T., Terracciano, A., Krueger, R. F., de Geus, E. J. C., Toshiko, T., Penninx, B. W. J. H., Esko, T., Madden, P. A. F., Derringer, J. L., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.128 · Cited by 370 · see citing works
Moskvina, V, Craddock, N., Holmans, P., Nikolov, I., Pahwa, J. S., Green, E., Wellcome Trust Case Control Consortium, Owen, M. J., & O'Donovan, M. C. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.133 · Cited by 363 · see citing works
Natural Variation in the Promoter of GSE5 Contributes to Grain Size Diversity in Rice
Duan, P., Xu, J., Zeng, D., Zhang, B., Geng, M., Zhang, G., Huang, K., Huang, L., Xu, R., Ge, S., et al. (2017) · Molecular Plant · doi:10.1016/j.molp.2017.03.009 · Cited by 363 · see citing works
Variation near complement factor I is associated with risk of advanced AMD
Fagerness, J. A., Maller, J. B., Neale, B. M., Reynolds, R. C., Daly, M. J., & Seddon, J. M. (2009) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.140 · Cited by 357 · see citing works
Tedja, M. S., Wojciechowski, R., Hysi, P. G., Eriksson, N., Furlotte, N. A., Verhoeven, V. J. M., Iglesias, A. I., Meester‐Smoor, M. A., Tompson, S. W. J., Fan, Q., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0127-7 · Cited by 352 · see citing works
Genome-Wide Pharmacogenetics of Antidepressant Response in the GENDEP Project
Uher, R., Perroud, N. A., Ng, M., Hauser, J., Henigsberg, N., Maier, W., Mors, O. N., Placentino, A., Rietschel, M., Souery, D., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09070932 · Cited by 350 · see citing works
Evans, L. M., Slavov, G. T., Rodgers‐Melnick, E., Martin, J., Ranjan, P., Muchero, W., Brunner, A. M., Schackwitz, W., Gunter, L. E., Chen, J., et al. (2014) · Nature Genetics · doi:10.1038/ng.3075 · Cited by 345 · see citing works
Christophersen, I. E., Rienstra, M., Roselli, C., Yin, X., Geelhoed, B., Barnard, J., Lin, H., Arking, D. E., Smith, A. V., Albert, C. M., et al. (2017) · Nature Genetics · doi:10.1038/ng.3843 · Cited by 339 · see citing works
Guidance for DNA methylation studies: statistical insights from the Illumina EPIC array
Mansell, G., Gorrie-Stone, T. J., Bao, Y., Kumari, M., Schalkwyk, L. S., Mill, J., & Hannon, E. (2019) · BMC Genomics · doi:10.1186/s12864-019-5761-7 · Cited by 340 · see citing works
Hysi, P. G., Choquet, H., Khawaja, A. P., Wojciechowski, R., Tedja, M. S., Yin, J., Simcoe, M. J., Patasova, K., Mahroo, O. A., Thai, K. K., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0599-0 · Cited by 333 · see citing works
Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis
Peters, U., Jiao, S., Schumacher, F. R., Hutter, C. M., Aragaki, A. K., Baron, J. A., Berndt, S. I., Bezieau, S., Brenner, H., Butterbach, K., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.12.020 · Cited by 321 · see citing works
Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder
An, J.-Y., Lin, K., Zhu, L., Werling, D. M., Dong, S., Brand, H., Wang, H. Z., Zhao, X., Schwartz, G. B., Collins, R. L., et al. (2018) · Science · doi:10.1126/science.aat6576 · Cited by 316 · see citing works
Genome-wide association meta-analysis identifies new endometriosis risk loci
Nyholt, D. R., Low, S.-K., Anderson, C. A., Painter, J. N., Uno, S., Morris, A. P., MacGregor, S., Gordon, S. D., Henders, A. K., Martin, N. G., et al. (2012) · Nature Genetics · doi:10.1038/ng.2445 · Cited by 315 · see citing works
Taylor, K. D., Norris, J. M., & Rotter, J. I. (2007) · Diabetes · doi:10.2337/db07-1324 · Cited by 307 · see citing works
The Role of Genetics in the Etiology of Schizophrenia
Gejman, P. V., Sanders, A. R., & Duan, J. (2010) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2009.12.003 · Cited by 292 · see citing works
Werling, D. M., Brand, H., An, J.-Y., Stone, M. R., Zhu, L., Glessner, J. T., Collins, R. L., Dong, S., Layer, R. M., Markenscoff-Papadimitriou, E., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0107-y · Cited by 293 · see citing works
Microbial genome-wide association studies: lessons from human GWAS
Power, R. A., Parkhill, J., & de Oliveira, T. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.132 · Cited by 274 · see citing works
So, H.-C., Gui, A. H. S., Cherny, S. S., & Sham, P. C. (2011) · Genetic Epidemiology · doi:10.1002/gepi.20579 · Cited by 289 · see citing works
Williams, H. J., Norton, N., Dwyer, S., Moskvina, V., Nikolov, I., Carroll, L. S., Georgieva, L., Williams, N. M., Morris, D. W., Quinn, E. M., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.36 · Cited by 279 · see citing works
Corvol, H., Blackman, S. M., Boëlle, P., Gallins, P. J., Pace, R. G., Stonebraker, J. R., Accurso, F. J., Clément, A., Collaco, J. M., Dang, H., et al. (2015) · Nature Communications · doi:10.1038/ncomms9382 · Cited by 277 · see citing works
Shyn, S. I., Shi, J., Kraft, J. B., Potash, J. B., Knowles, J. A., Weissman, M. M., Garriock, H. A., Yokoyama, J. S., McGrath, P. J., Peters, E. J., et al. (2009) · Molecular Psychiatry · doi:10.1038/mp.2009.125 · Cited by 270 · see citing works
Genome-wide association study of recurrent early-onset major depressive disorder
Shi, J., Potash, J. B., Knowles, J. A., Weissman, M. M., Coryell, W. H., Scheftner, W. A., Lawson, W. B., DePaulo, J. R., Gejman, P. V., Sanders, A. R., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.124 · Cited by 267 · see citing works
Genome-wide Association Scan of Attention Deficit Hyperactivity Disorder
Neale, B., Su, J., Anney, R., Franke, B., Zhou, K., Maller, J., Vásquez, A., Asherson, P., Chen, W., Banaschewski, T., et al. (2008) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30866 · Cited by 288 · see citing works
The meta-analysis of genome-wide association studies
Thompson, J. R., Attia, J., & Minelli, C. (2011) · Briefings in Bioinformatics · doi:10.1093/bib/bbr020 · Cited by 250 · see citing works
BMES GWAS Group, Hysi, P. G., Cheng, C., Springelkamp, H., MacGregor, S., Bailey, J. N. C., Wojciechowski, R., Vitart, V., Nag, A., Hewitt, A. W., et al. (2014) · Nature Genetics · doi:10.1038/ng.3087 · Cited by 249 · see citing works
Improving the odds of drug development success through human genomics: modelling study
Hingorani, A. D., Kuan, V., Finan, C., Krüger, F. A., Gaulton, A., Chopade, S., Sofat, R., MacAllister, R. J., Overington, J. P., Hemingway, H., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-54849-w · Cited by 242 · see citing works
GENDEP Investigators, MARS Investigators, STAR*D Investigators, Uher, R., Tansey, K. E., Henigsberg, N., Wolfgang, M. C., Mors, O. N., Hauser, J., Placentino, A., et al. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12020237 · Cited by 241 · see citing works
Rafi, Z., & Greenland, S. (2020) · BMC Medical Research Methodology · doi:10.1186/s12874-020-01105-9 · Cited by 243 · see citing works
Overview of Statistical Methods for Genome-Wide Association Studies (GWAS)
Hayes, B. J. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-447-0_6 · Cited by 243 · see citing works
Genome-Wide Association Study of Major Recurrent Depression in the U.K. Population
Lewis, C. M., Ng, M., Butler, A. W., Cohen‐Woods, S., Uher, R., Pirlo, K. J., Weale, M. E., Schosser, A., Paredes, U. M., Rivera, M., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09091380 · Cited by 237 · see citing works
Liu, D. J., & Leal, S. M. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001156 · Cited by 236 · see citing works
The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression
Kohli, M. A., Lucae, S., Saemann, P. G., Schmidt, M. V., Demirkan, A., Hek, K., Czamara, D., Alexander, M., Salyakina, D., Ripke, S., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.005 · Cited by 228 · see citing works
Lindström, S., Wang, L., Smith, E. N., Gordon, W., van Hylckama Vlieg, A., de Andrade, M., Brody, J. A., Pattee, J. W., Haessler, J., Brumpton, B. M., et al. (2019) · Blood · doi:10.1182/blood.2019000435 · Cited by 223 · see citing works
Correction: Power and Predictive Accuracy of Polygenic Risk Scores
Dudbridge, F. (2013) · PLoS Genetics · doi:10.1371/annotation/b91ba224-10be-409d-93f4-7423d502cba0 · Cited by 220 · see citing works
Self-citationA Global In Vivo Drosophila RNAi Screen Identifies NOT3 as a Conserved Regulator of Heart Function
Neely, G. G., Kuba, K., Cammarato, A., Isobe, K., Amann, S., Zhang, L., Murata, M., Elmeń, L., Gupta, V., Arora, S., et al. (2010) · Cell · doi:10.1016/j.cell.2010.02.023 · Cited by 218 · see citing works
Genome‐wide association studies of cerebral white matter lesion burden
Fornage, M., Debette, S., Bis, J. C., Schmidt, H., Ikram, M. A., Dufouil, C., Sigurdsson, S. O., Lumley, T., DeStefano, A. L., Fazekas, F., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22403 · Cited by 220 · see citing works
Genetics of psychosis; insights from views across the genome
O’Donovan, M. C., Craddock, N. J., & Owen, M. J. (2009) · Human Genetics · doi:10.1007/s00439-009-0703-0 · Cited by 213 · see citing works
Duggal, P., Thio, C. L., Wojcik, G. L., Goedert, J. J., Mangia, A., Latanich, R., Kim, A. Y., Lauer, G. M., Chung, R. T., Peters, M. G., et al. (2013) · Annals of Internal Medicine · doi:10.7326/0003-4819-158-4-201302190-00003 · Cited by 214 · see citing works
Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations
Hicks, A. A., Pramstaller, P. P., Johansson, Å., Vitart, V., Rudan, I., Ugocsai, P., Aulchenko, Y. S., Franklin, C. S., Liebisch, G., Erdmann, J., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000672 · Cited by 214 · see citing works
The genetics of Tourette syndrome: A review
O'Rourke, J. A., Scharf, J. M., Yu, D., & Pauls, D. L. (2009) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2009.06.006 · Cited by 212 · see citing works
Hsu, Y., Zillikens, M. C., Wilson, S. G., Farber, C. R., Demissie, S., Soranzo, N., Bianchi, E. N., Grundberg, E., Liang, L., Richards, J. B., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000977 · Cited by 210 · see citing works
Genome-wide association study of Tourette's syndrome
Scharf, J. M., Yu, D., Mathews, C. A., Neale, B. M., Stewart, S. E., Fagerness, J. A., Evans, P. D., Gamazon, E. R., Edlund, C. K., Service, S. K., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.69 · Cited by 211 · see citing works
Chen, D. T., Jiang, X., Akula, N., Shugart, Y. Y., Wendland, J. R., Steele, C. J. M., Kassem, L., Park, J.-H., Chatterjee, N., Jamain, S., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.157 · Cited by 208 · see citing works
A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder
Wang, K.-S., Liu, X.-F., & Aragam, N. (2010) · Schizophrenia Research · doi:10.1016/j.schres.2010.09.002 · Cited by 204 · see citing works
Meta-analysis of new genome-wide association studies of colorectal cancer risk
Peters, U., Hutter, C. M., Hsu, L., Schumacher, F. R., Conti, D. V., Carlson, C. S., Edlund, C. K., Haile, R. W., Gallinger, S., Zanke, B. W., et al. (2011) · Human Genetics · doi:10.1007/s00439-011-1055-0 · Cited by 207 · see citing works
Paterson, A. D., Lopes-Virella, M. F., Waggott, D. M., Boright, A. P., Hosseini, S. M., Carter, R. E., Enqing, S., Mirea, L., Bharaj, B., Sun, L., et al. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.192971 · Cited by 206 · see citing works
Sun, L., Rommens, J. M., Corvol, H., Li, W., Li, X., Chiang, T., Fan, L., Dorfman, R., Busson, P., Parekh, R. V., et al. (2012) · Nature Genetics · doi:10.1038/ng.2221 · Cited by 201 · see citing works
Coleman, J. R. I., Peyrot, W. J., Purves, K. L., Davis, K. A. S., Rayner, C., Choi, S. W., Hübel, C., Gaspar, H. A., Kan, C., der Auwera, S. V., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0546-6 · Cited by 195 · see citing works
Obesity genetics in mouse and human: back and forth, and back again
Yazdi, F., Clee, S. M., & Meyre, D. (2015) · PeerJ · doi:10.7717/peerj.856 · Cited by 197 · see citing works
Methodological challenges of genome-wide association analysis in Africa
Teo, Y., Small, K. S., & Kwiatkowski, D. P. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2731 · Cited by 195 · see citing works
Taylor, A. E., Jones, H. J., Sallis, H., Euesden, J., Stergiakouli, E., Davies, N. M., Zammit, S., Lawlor, D. A., Munafò, M. R., Davey Smith, G., et al. (2018) · International Journal of Epidemiology · doi:10.1093/ije/dyy060 · Cited by 192 · see citing works
Williams, H. J., Craddock, N. J., Russo, G., Hamshere, M. L., Moskvina, V., Dwyer, S., Smith, R., Green, E., Grozeva, D., Holmans, P., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq471 · Cited by 189 · see citing works
Genetics of schizophrenia: new findings and challenges
Gejman, P. V., Sanders, A. R., & Kendler, K. S. (2011) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082410-101459 · Cited by 183 · see citing works
Estimation of a significance threshold for epigenome-wide association studies
Saffari, A., Silver, M. J., Zavattari, P., Moi, L., Columbano, A., Meaburn, E. L., & Dudbridge, F. (2018) · Genetic Epidemiology · doi:10.1002/gepi.22086 · Cited by 183 · see citing works
Self-citationTMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies
Erhardt, A., Czibere, L., Roeske, D., Lucae, S., Unschuld, P. G., Ripke, S., Specht, M., Kohli, M. A., Kloiber, S. M., Ising, M., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.41 · Cited by 182 · see citing works
McMahon, F. J., Akula, N., Schulze, T. G., Detera‐Wadleigh, S. D., Steele, C. J. M., Wendland, J. R., Breuer, R., Strohmaier, J., Rietschel, M., Muglia, P., et al. (2010) · Nature Genetics · doi:10.1038/ng.523 · Cited by 179 · see citing works
Revisiting the genome-wide significance threshold for common variant GWAS
Chen, Z., Boehnke, M., Wen, X., & Mukherjee, B. (2021) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkaa056 · Cited by 179 · see citing works
Han, B., Kang, H. M., & Eskin, E. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000456 · Cited by 175 · see citing works
Genome-Wide Association Study of Schizophrenia in a Japanese Population
Ikeda, M., Aleksić, B., Kinoshita, Y., Okochi, T., Kawashima, K., Kushima, I., Ito, Y., Nakamura, Y., Kishi, T., Okumura, T., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.07.010 · Cited by 172 · see citing works
Estimation and Partition of Heritability in Human Populations Using Whole-Genome Analysis Methods
Vinkhuyzen, A. A. E., Wray, N. R., Yang, J., Goddard, M. E., & Visscher, P. M. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-111212-133258 · Cited by 167 · see citing works
Genetics of bipolar disorder: successful start to a long journey
Craddock, N. J., & Sklar, P. B. (2009) · Trends in Genetics · doi:10.1016/j.tig.2008.12.002 · Cited by 166 · see citing works
Verweij, K. J. H., Zietsch, B. P., Medland, S. E., Gordon, S. D., Benyamin, B., Nyholt, D. R., McEvoy, B. P., Sullivan, P. F., Heath, A. C., Madden, P. A. F., et al. (2010) · Biological Psychology · doi:10.1016/j.biopsycho.2010.07.018 · Cited by 166 · see citing works
Peerbooms, O., van Os, J., Drukker, M., Kenis, G., Hoogveld, L., Binder, M. D., Delespaul, P., van Winkel, R., & Rutten, B. P. F. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.12.006 · Cited by 162 · see citing works
Case-Control Genome-Wide Association of Attention-Deficit / Hyperactivity Disorder
Neale, B., Medland, S., Ripke, S., Anney, R., Asherson, P., Buitelaar, J., Franke, B., Gill, M., Kent, L., Holmans, P., et al. (2010) · Journal of the American Academy of Child and Adolescent Psychiatry · doi:10.1016/j.jaac.2010.06.007 · Cited by 175 · see citing works
A genome-wide association study of attempted suicide
Willour, V. L., Seifuddin, F., Mahon, P. B., Jancic, D., Pirooznia, M., Steele, J., Schweizer, B. W., Goes, F. S., Mondimore, F. M., MacKinnon, D. F., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.4 · Cited by 162 · see citing works
Biostatistical Aspects of Genome‐Wide Association Studies
Ziegler, A., König, I. R., & Thompson, J. R. (2008) · Biometrical Journal · doi:10.1002/bimj.200710398 · Cited by 159 · see citing works
Assessing the Heritability of Complex Traits in Humans: Methodological Challenges and Opportunities
Mayhew, A., & Meyre, D. (2017) · Current Genomics · doi:10.2174/1389202918666170307161450 · Cited by 159 · see citing works
- Authors
- Dudbridge, F., & Gusnanto, A.
- Affiliations
- MRC Biostatistics Unit (GB)
- Corresponding author
- Dudbridge, Frank
- Venue
- Genetic Epidemiology
- Publisher
- Wiley
- Published
- 2008-02-25
- Volume
- 32
- Issue
- 3
- Pages
- 227-234
- ISSN
- 0741-0395 (ISSN-L)
- 1098-2272
- PMC
- PMC2573032
- OpenAlex
- W2105239414
- Cited by
- 703
- References
- 26
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 26 · 2023: 30 · 2022: 26 · 2021: 36 · 2020: 45 · 2019: 32 · 2018: 49 · 2017: 32 · 2016: 30 · 2015: 36 · 2014: 47 · 2013: 47 · 2012: 46
- FWCI
- 33.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genetic Epidemiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Funders
- Sixth Framework Programme (LSHM-CT-2004-503485)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- 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 diversity and population structure
- Keywords
- genome-wide association study, permutation tests, family-wise error rate, multiple testing correction, subsampling, beta distribution, Wellcome Trust Case Control Consortium
- MeSH terms
- Genetic Markers, Genotype, United Kingdom, Humans, Genome, Human, Case-Control Studies, Genetic Predisposition to Disease, White People
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
