The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Genomic Control for Association Studies
Abstract
Summary. A dense set of single nucleotide polymorphisms (SNP) covering the genome and an efficient method to assess SNP genotypes are expected to be available in the near future. An outstanding question is how to use these technologies efficiently to identify genes affecting liability to complex disorders. To achieve this goal, we propose a statistical method that has several optimal properties: It can be used with case‐control data and yet, like family‐based designs, controls for population heterogeneity; it is insensitive to the usual violations of model assumptions, such as cases failing to be strictly independent; and, by using Bayesian outlier methods, it circumvents the need for Bonferroni correction for multiple tests, leading to better performance in many settings while still constraining risk for false positives. The performance of our genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders.
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In the citing paper
“the conventional genomic inflation factor (lambda or λ used interchangeably below) is dependent on the expected number of true associations”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [31]
In the citing paper
“Because in a typical epigenome-wide association study (EWAS), it is expected that small effects from many CpGs might be associated with the phenotype, the genomic inflation factor would overestimate actual test-statistic inflation”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [31]
In the citing paper
“The genomic control inflation factor (λ) 11 was 1.037, suggesting little evidence for residual stratification.”
From Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease (2009) · cites this paper as [11]
In the citing paper
“The most popular are genomic control (GC)21,22, principal component analysis (PCA)23 and linear mixed models24.”
From Differential confounding of rare and common variants in spatially structured populations (2012) · cites this paper as [22]
In the citing paper
“The overall inflation of the results due to population stratification is negligible: a modified [7] genomic control factor [10] (see Text S1).”
From Integrated Model of De Novo and Inherited Genetic Variants Yields Greater Power to Identify Risk Genes (2013) · cites this paper as [10]
In the citing paper
“Prior to the gene-based analyses all individual SNP P-values were corrected for the genomic inflation factor (λ; to normalise for unaccounted variation, due to factors such as population stratification; Devlin and Roeder, 1999).”
From Genetic variability in response to amyloid beta deposition influences Alzheimer’s disease risk (2019) · cites this paper as Devlin and Roeder, 1999
In the citing paper
“Residual stratification was further corrected at the meta-analytic level with study-specific genomic controls56”
From Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use (2019) · cites this paper as [56]
In the citing paper
“For the discovery, we applied two rounds of genomic control corrections to each individual GWAS and the combined meta results, respectively 51.”
From Seven new loci associated with age-related macular degeneration (2013) · cites this paper as [51]
In the citing paper
“Methods were developed to detect and adjust for such biases (67–69) as well as unexpected relatedness between subjects.”
From Genetic Mapping in Human Disease (2008) · cites this paper as [67]
Citations
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Enjuanes, A., Benavente, Y., Bosch, F., Martín‐Guerrero, I., Colomer, D., Pérez-Álvarez, S., Reina, Ó., Ardanaz, M. T., Jares, P., García‐Orad, Á., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-2221 · Cited by 72
“to estimate quantitatively the amount of population stratification (22).”
BackgroundMarroni, F., Pfeufer, A., Aulchenko, Y. S., Franklin, C. S., Isaacs, A. J., Pichler, I., Wild, S. H., Oostra, B. A., Wright, A. F., Campbell, H., et al. (2009) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.108.833806 · Cited by 72
Chen, H., Zhu, X., Zhao, H., & Zhang, S. (2003) · Annals of Human Genetics · doi:10.1046/j.1469-1809.2003.00036.x · Cited by 71
“In addition, QualSPT is much more powerful than the GC method (Devlin & Roeder, 1999; Bacanu et al. 2000) when population stratification is strong.”
MethodInfluentialStyrkársdóttir, U., Þorleifsson, G., Gudjonsson, S. A., Sigurðsson, Á., Lee, S. H., Nguyen, T. V., Kwok, T. C. Y., Lee, J. S. W., Ho, S. C., Woo, J., et al. (2016) · Nature Communications · doi:10.1038/ncomms10129 · Cited by 72
Susceptibility to corticosteroid-induced adrenal suppression: a genome-wide association study
Hawcutt, D. B., Francis, B., Carr, D. F., Jorgensen, A., Yin, P., Wallin, N., O'Hara, N., Zhang, E. J., Bloch, K. M., Ganguli, A., et al. (2018) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(18)30058-4 · Cited by 72
Bustos‐Korts, D., Dawson, I. K., Russell, J., Tondelli, A., Guerra, D., Ferrandi, C., Strozzi, F., Nicolazzi, E. L., Molnár‐Láng, M., Özkan, H., et al. (2019) · The Plant Journal · doi:10.1111/tpj.14414 · Cited by 71
“The significance threshold employed for testing marker–trait associations was established using a Bonferroni correction for independently segregating chromosome segments (Li and Ji, 2005) in combination with a correction for genomic control (Devlin and Roeder, 1999; Kang et al., 2008).”
MethodMandaviya, P. R., Joehanes, R., Brody, J. A., Fernandez, J. C., Dekkers, K. F., Do, A. N., Graff, M., Hänninen, I. K., Tanaka, T., de Jonge, E. A., et al. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz031 · Cited by 76
“The genomic inflation factors (39) were computed to estimate the rate of false positives due to population structure.”
MethodLee, J. J., McGue, M., Iacono, W. G., & Chow, C. C. (2018) · Genetic Epidemiology · doi:10.1002/gepi.22161 · Cited by 79
“This simple and insightful method of estimating the average χ2 statistic of truly null SNPs (or at least a certain subset of such SNPs) should in most cases lead to a much better global correction of the association statistics than the overly conservative genomic control (Devlin & Roeder, 1999).”
MethodAlthouse, A. D., Below, J. E., Claggett, B. L., Cox, N. J., de Lemos, J. A., Deo, R. C., Duval, S., Hachamovitch, R., Kaul, S., Keith, S. W., et al. (2021) · Circulation · doi:10.1161/circulationaha.121.055393 · Cited by 74
Malovini, A. L., Illario, M., Iaccarino, G., Villa, F., Ferrario, A., Roncarati, R., Anselmi, C. V., Novelli, V., Cipolletta, E., Leggiero, E., et al. (2011) · Rejuvenation Research · doi:10.1089/rej.2010.1114 · Cited by 72
“1) and the estimated genomic inflation factor ( l ) 24 for the different genetic models revealed a moderate residual effect of population stratification on the association results (allelic l , 1.09; dominant l , 1.07; recessive l , 1.00).”
InfluentialGenetics of abdominal aortic aneurysm
Golledge, J., & Kuivaniemi, H. (2013) · Current Opinion in Cardiology · doi:10.1097/hco.0b013e32835f0d55 · Cited by 72
Folate metabolic gene polymorphisms and childhood acute lymphoblastic leukemia: a case–control study
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“Although the German population is probably genetically homogeneous, we used a genomic control approach to assess population stratification”
MethodChanges in food reward following smoking cessation: a pharmacogenetic investigation
Lerman, C. E., Berrettini, W. H., Pinto, A. G., Patterson, F., Crystal-Mansour, S., Wileyto, E. P., Restine, S., Leonard, D. G. B., Shields, P., & Epstein, L. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1823-9 · Cited by 71
“To assess the potential for population stratification, we used the method for genomic control described previously by Devlin and Roeder (1999).”
InfluentialRedden, D. T., Divers, J., Vaughan, L. K., Tiwari, H. K., Beasley, T. M., Fernández, J. R., Kimberly, R. P., Feng, R., Padilla, M. A., Liu, N., et al. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0020137 · Cited by 71
“the population structure [14,18,19].”
Sanchez, M.-P., Tribout, T., Iannuccelli, N., Bouffaud, M., Servin, B., Tenghe, A., Déhais, P., Muller, N., Schneider, M. D. P., Mercat, M.-J., et al. (2014) · Genetics Selection Evolution · doi:10.1186/1297-9686-46-12 · Cited by 71
“The P-values were then corrected by multiplying observed P-values by the regression factor λ, using the genomic control method [27].”
Weber, A., Clark, R. M., Vaughn, L., González, J. D. J. S., Yu, J., Yandell, B. S., Bradbury, P. J., & Doebley, J. (2007) · Genetics · doi:10.1534/genetics.107.080424 · Cited by 71
“…multiple analytical methods to reduce the frequency of false-positive associations such as using genomic control to adjust the raw test statistic (Devlin and Roeder 1999), incorporation of population structure into a likelihood-ratio test comparing the likelihood of the null hypothesis of…”
MethodSchork, N. J., Nath, S. K., Fallin, D., & Chakravarti, A. (2000) · The American Journal of Human Genetics · doi:10.1086/321201 · Cited by 86
“An additional issue that plagues LDmapping studies of quantitative traits is population stratification and cryptic heterogeneity, which, fortunately, can be dealt with for analyses involving quantitative traits in a manner analogous to the methods used for qualitative traits (see, e.g., Devlin and Roeder [1999] , Prit…”
MethodDiscovery and Fine Mapping of Serum Protein Loci through Transethnic Meta-analysis
Franceschini, N., van Rooij, F. J. A., Prins, B. P., Feitosa, M. F., Karakas, M., Eckfeldt, J. H., Folsom, A. R., Kopp, J. B., Vaez, A., Andrews, J. S., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.08.021 · Cited by 70
“The results of each GWAS were corrected for residual population structure using the genomic control inflation factor 11 and were combined via fixed-effect inverse-variance-weighted meta-analysis.”
Ohtsuki, T., Koga, M., Ishiguro, H., Horiuchi, Y., Arai, M., Niizato, K., Itokawa, M., Inada, T., Iwata, N., Iritani, S., et al. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.01.027 · Cited by 70
“Genotypic associations were examined by Armitage's Trend Test for the reasons discussed by Devlin and Roeder (Devlin and Roeder 1999).”
MethodFletcher, J. M., & Conley, D. (2013) · American Journal of Public Health · doi:10.2105/ajph.2013.301290 · Cited by 70
Modulation of cystic fibrosis lung disease by variants in interleukin-8
Hillian, A. D., Londoño, D., Dunn, J. M., Goddard, K. A. B., Pace, R. G., Knowles, M. R., & Drumm, M. L. (2008) · Genes and Immunity · doi:10.1038/gene.2008.42 · Cited by 69
Schlauch, K. A., Khaiboullina, S. F., Meirleir, K. L. D., Rawat, S., Petereit, J., Rizvanov, A. A., Blatt, N. L., Mijatovic, T., Kulick, D., Palotás, A., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2015.208 · Cited by 71
Havlíčková, L., He, Z., Wang, L., Langer, S., Harper, A. L., Kaur, H., Broadley, M. R., Gegas, V. C., & Bancroft, I. (2017) · The Plant Journal · doi:10.1111/tpj.13767 · Cited by 70
“Genomic control (Devlin and Roeder, 1999) was applied to the GEM analysis to correct for spurious associations, with P-value adjustment applied when the genomic inflation factor (k) was observed to be greater than 1.”
MethodHagenblad, J., Tang, C., Molitor, J., Werner, J. D., Zhao, K., Zheng, H., Marjoram, P., Weigel, D., & Nordborg, M. (2004) · Genetics · doi:10.1534/genetics.104.029470 · Cited by 69
Genetic Association Analysis Using Data from Triads and Unrelated Subjects
Epstein, M. P., Veal, C., Trembath, R. C., Barker, J. N. W. N., Li, C., & Satten, G. A. (2005) · The American Journal of Human Genetics · doi:10.1086/429225 · Cited by 70
“If hidden population substructure exists, one can correct the bias in statistical tests by using genotype information from unlinked markers (Devlin and Roeder 1999; Pritchard et al. 2000; Satten et al. 2001).”
MethodGenome-Wide Association Analysis of Age-Dependent Egg Weights in Chickens
Liu, Z., Sun, C., Yan, Y., Li, G., Wu, G., Liu, A., & Yang, N. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00128 · Cited by 69
“A genomic inflation factor (λ) was also calculated using the “GenABEL” package in R (Devlin, 1999) to evaluate the extent of false positive signals.”
Polygenic Scores in Epidemiology: Risk Prediction, Etiology, and Clinical Utility
Maher, B. S. (2015) · Current Epidemiology Reports · doi:10.1007/s40471-015-0055-3 · Cited by 69
Lange, L. A., Croteau‐Chonka, D. C., Marvelle, A. F., Li, Q., Gaulton, K. J., Kuzawa, C. W., McDade, T. W., Wang, Y., Li, Y., Levy, S., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq062 · Cited by 69
“Finally, we examined the calculated genomic control value to evaluate for systematic P-value inflation due to cryptic relatedness between samples not accounted for by the analytic adjustment for PCs in the regression analyses (34).”
MethodInterrogating local population structure for fine mapping in genome-wide association studies
Qin, H., Morris, N. J., Kang, S. J., Li, M., Tayo, B. O., Lyon, H. N., Hirschhorn, J. N., Cooper, R., & Zhu, X. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq560 · Cited by 69
“A popular procedure to eliminate the effect of population structure is the genomic control (GC) approach (Devlin and Roeder, 1999), which assumes that the variance inflation factor of a test statistic is a constant across the genome.”
BackgroundFamily-Based versus Unrelated Case-Control Designs for Genetic Associations
Εvangelou, Ε., Trikalinos, T. A., Salanti, G., & Ioannidis, J. P. A. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020123 · Cited by 69
“]. A number of approaches have been proposed to try to detect and account for population stratification in population based studies [”
BackgroundGenome-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
“S4), is consistent with the expectation for such analyses, and the genomic control estimate [75], GC= 1.”
ResultSelf-citationCheng, S., Xu, Z., Bian, S., Chen, X., Shi, Y., Li, Y., Duan, Y., Liu, Y., Lin, J., Jiang, Y., et al. (2023) · Cell Discovery · doi:10.1038/s41421-023-00582-8 · Cited by 71
Significant association between toll-like receptor gene polymorphisms and gallbladder cancer
Srivastava, K., Srivastava, A., Kumar, A., & Mittal, B. (2010) · Liver International · doi:10.1111/j.1478-3231.2010.02268.x · Cited by 68
“To test the possibility for population stratification, genomic control method was used as described by Devlin and Roeder (12).”
MethodLi, Y., Böck, A., Haseneyer, G., Korzun, V. N., Wilde, P., Schön, C., Ankerst, D. P., & Bauer, E. (2011) · BMC Plant Biology · doi:10.1186/1471-2229-11-146 · Cited by 68
“In response, several advanced statistical approaches have been developed for genotype-phenotype association studies, including genomic control [36], structured association [37], and linear mixed model-based methodologies [38,39].”
MethodGenetic Susceptibility to Peripheral Arterial Disease: A Dark Corner in Vascular Biology
Knowles, J. W., Assimes, T. L., Li, J. Z., Quertermous, T., & Cooke, J. P. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000282199.66398.8c · Cited by 68
Genome-Wide Association Study of Young-Onset Hypertension in the Han Chinese Population of Taiwan
Yang, H., Liang, Y.-J., Wu, Y.-L., Chung, C.-M., Chiang, K.-M., Ho, H., Ting, C.-T., Lin, T., Sheu, S., Tsai, W.-C., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005459 · Cited by 68
“Second, we evaluated population admixture of the Taiwanese population by using STRUCTURE software [21] and genomic control analyses [22].”
MethodWebb, E. L., Rudd, M. F., Sellick, G. S., Galta, R. E., Bethke, L., Wood, W., Fletcher, O., Penegar, S., Withey, L., Qureshi, M., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl401 · Cited by 68
Ingle, J. N., Liu, M., Wickerham, D. L., Schaid, D. J., Wang, L., Mushiroda, T., Kubo, M., Costantino, J. P., Vogel, V. G., Paik, S., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0038 · Cited by 68
Genome-Wide Association Study on Resistance to Stalk Rot Diseases in Grain Sorghum
Adeyanju, A., Little, C. R., Yu, J., & Tesso, T. (2015) · G3 Genes Genomes Genetics · doi:10.1534/g3.114.016394 · Cited by 68
“This concern is usually addressed using general linear model (GLM)-based methods such as structured association (Pritchard et al. 2000), genomic control (Devlin and Roeder 1999), and family-based tests of association (Abecasis et al. 2000).”
BackgroundMethodMixed Model with Correction for Case-Control Ascertainment Increases Association Power
Hayeck, T. J., Zaitlen, N., Loh, P., Vilhjálmsson, B. J., Pollack, S. J., Gusev, A., Yang, J., Chen, G., Goddard, M. E., Visscher, P. M., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.03.004 · Cited by 65
Roschanski, A. M., Csilléry, K., Liepelt, S., Oddou-Muratorio, S., Ziegenhagen, B., Huard, F., Ullrich, K., Postolache, D., Vendramin, G., & Fady, B. (2016) · Molecular Ecology · doi:10.1111/mec.13516 · Cited by 71
“© 2015 John Wiley & Sons Ltd of the false discovery rate due to multiple testing, and it is defined as the ratio of the observed and the expected median of the distribution of the test statistic (Devlin & Roeder 1999). k was estimated as median (Z²)/0.456.”
BackgroundInfluentialShared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms
Hof, F. N. G. V. ’., Ruigrok, Y. M., Lee, C. H., Ripke, S., Anderson, G., de Andrade, M., Baas, A. F., Blankensteijn, J. D., Böttinger, E. P., Bown, M. J., et al. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.115.002603 · Cited by 68
“We calculated genomic inflation factors (kGC) for each GWAS and the mega-analysis, defined as the ratio of the median of the empirically observed distribution of the test statistic to the expected median.(29) We calculated the statistical power for detecting a significant association (P<5910 (8)) in the mega-analysis…”
MethodProfiling and Leveraging Relatedness in a Precision Medicine Cohort of 92,455 Exomes
Staples, J. C., Maxwell, E. K., Gosalia, N., Gonzaga-Jauregui, C. G., Snyder, C., Hawes, A. C., Penn, J., Ulloa, R. H., Bai, X., Lopez, A. E., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.03.012 · Cited by 66
Africans and Asians abroad: genetic diversity in Europe.
Barbujani, G., & Goldstein, D. (2004) · Annual review of genomics and human genetics (Print) · doi:10.1146/annurev.genom.5.061903.180021 · Cited by 73
“If there was stratification involving individuals of African and European ancestry, for example, most polymorphisms in the genome could show significant differences for any disease that differs in incidence between Africa and Europe (47).”
BackgroundGenetic determinants of the inflammatory response
Imahara, S. D., & O’Keefe, G. E. (2004) · Current Opinion in Critical Care · doi:10.1097/01.ccx.0000140942.42247.7e · Cited by 67
Lampis, R. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.20.2959 · Cited by 67
Genome-Wide Association Analyses Identify SPOCK as a Key Novel Gene Underlying Age at Menarche
Liu, Y.-Z., Guo, Y.-F., Wang, L., Tan, L.-J., Liu, X.-G., Pei, Y.-F., Yan, H., Xiong, D.-H., Deng, F., Yu, N., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000420 · Cited by 68
“2, we further tested population stratification of our GWAS Cohort using a method of genomic control [28].”
MethodSerotonin transporter polymorphism and borderline or antisocial traits among low-income young adults
Lyons-Ruth, K., Holmes, B. M., Sasvari-Szekely, M., Ronai, Z., Nemoda, Z., & Pauls, D. (2007) · Psychiatric Genetics · doi:10.1097/ypg.0b013e3281ac237e · Cited by 67
“of spurious association due to sample heterogeneity was assessed by genomic control (Devlin and Roeder, 1999), analyzing 40 random marker polymorphisms distributed evenly along the human genome (1–3 markers per chromosome).”
BackgroundOne potato, two potato: haplotype association mapping in autotetraploids
Šimko, I. (2004) · Trends in Plant Science · doi:10.1016/j.tplants.2004.07.003 · Cited by 68
Prospects for Association Mapping in Classical Inbred Mouse Strains
Payseur, B. A., & Place, M. (2007) · Genetics · doi:10.1534/genetics.106.067868 · Cited by 67
“Fortunately, several methods have been developed that adjust for the effects of population structure on association mapping using patterns of variation at unlinked markers (Devlin and Roeder 1999; Pritchard et al. 2000; Reich and Goldstein 2001; Yu et al. 2006).”
MethodUGT1A1 is a major locus influencing bilirubin levels in African Americans
Chen, G., Ramos, E., Adeyemo, A., Shriner, D., Zhou, J., Doumatey, A. P., Huang, H., Erdos, M. R., Gerry, N. P., Herbert, A. G., et al. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2011.206 · Cited by 69
“We estimated the genomic inflation factor ( λ GC ) based on the median chi-squared test of all study participants”
Methodde Quervain, D. J. ‐., Kolassa, I., Ackermann, S., Aerni, A., Boesiger, P., Demougin, P., Elbert, T. R., Ertl, V., Gschwind, L., Hadziselimovic, N. O., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200857109 · Cited by 69
“We also applied the Genomic Control program that is implemented in the EIGENSTRAT package to compute the inflation factor λ (38).”
MethodQuality Control Procedures for Genome‐Wide Association Studies
Truong, V. Q., Woerner, J., Cherlin, T., Bradford, Y., Lucas, A., Okeh, C. C., Shivakumar, M., Hui, D. H., Kumar, R., Pividori, M., et al. (2022) · Current Protocols · doi:10.1002/cpz1.603 · Cited by 71
“Genomic control (Devlin & Roeder, 1999; Reich & Goldstein, 2001) aims to account for population stratification by first estimating an inflation factor (λ), then adjusting all of the test statistics downward by this factor.”
BackgroundBarnholtz-Sloan, J., Mcevoy, B. P., Shriver, M., & Rebbeck, T. (2008) · Cancer Epidemiology, Biomarkers and Prevention · doi:10.1158/1055-9965.epi-07-0491 · Cited by 70
“Genomic control was one of the first methods developed to adjust for population stratification (41-44).”
MethodReporting and interpretation in genome-wide association studies
Wakefield, J. (2008) · International Journal of Epidemiology · doi:10.1093/ije/dym257 · Cited by 67
Li, M., Luo, X.-J., Rietschel, M., Lewis, C. M., Mattheisen, M., Müller-Myhsok, B., Jamain, S., Leboyer, M., Landén, M., Thompson, P. M., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.37 · Cited by 65
“26 With the exception of the Icelandic group, the genomic inflation factors ( l ) were all o 1.1.”
InfluentialSkotte, L., Fadista, J., Bybjerg‐Grauholm, J., Appadurai, V., Hildebrand, M. S., Hansen, T. F., Banasik, K., Grove, J., Albiñana, C., Geller, F., et al. (2021) · Brain · doi:10.1093/brain/awab260 · Cited by 67
“23 To assess possible confounding effects on the distribution of test statistics, we calculated the genomic inflation factor 24 and the linkage disequilibrium (LD) score regression intercept.”
Convergent Genomic Studies Identify Association of GRIK2 and NPAS2 with Chronic Fatigue Syndrome
Smith, A. K., Fang, H., Whistler, T., Unger, E. R., & Rajeevan, M. S. (2011) · Neuropsychobiology · doi:10.1159/000326692 · Cited by 67
Sharma, K. L., Misra, S., Kumar, A., & Mittal, B. (2012) · Liver International · doi:10.1111/j.1478-3231.2012.02822.x · Cited by 66
Höglund, J., Sahana, G., Guldbrandtsen, B., & Lund, M. S. (2014) · BMC Genetics · doi:10.1186/1471-2156-15-8 · Cited by 69
“The lambda-values that reflect the genome-wide inflation of the test statistics [29] ranged from 2.6 to 4.7 for different traits.”
InfluentialAdjustment for local ancestry in genetic association analysis of admixed populations
Wang, X., Zhu, X., Qin, H., Cooper, R., Ewens, W. J., Li, C., & Li, M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq709 · Cited by 66
Guo, J., Jorjani, H., & Carlborg, Ö. (2012) · BMC Genetics · doi:10.1186/1471-2156-13-82 · Cited by 73
“So far, several different methods to correct for systematic confounding have been proposed [21-23].”
BackgroundMethodInfluentialDopamine D2 receptor gene Ser311Cys variant and schizophrenia: association study and meta‐analysis
Jönsson, E. G., Sillén, A., Vares, M., Ekholm, B., Terenius, L. Y., & Sedvall, G. C. (2003) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.20004 · Cited by 66
“Methodologies to control for population stratification in materials of unrelated subjects have recently emerged, but were not applied in the present study [Devlin and Roeder, 1999; Bacanu et al., 2000; Pritchard et al., 2000].”
MethodGenetic Variants Associated with Circulating Parathyroid Hormone
Robinson‐Cohen, C., Lutsey, P. L., Kleber, M. E., Nielson, C. M., Mitchell, B. D., Bis, J. C., Eny, K. M., Portas, L., Eriksson, J., Lorentzon, M., et al. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016010069 · Cited by 66
Systemic sclerosis: the susceptible host (genetics and environment)
Tan, F. K. (2003) · Rheumatic Disease Clinics of North America · doi:10.1016/s0889-857x(03)00015-2 · Cited by 64
Li, Y., Schrodi, S. J., Rowland, C. M., Tacey, K. M., Catanese, J. J., & Grupe, A. (2006) · Human Mutation · doi:10.1002/humu.20382 · Cited by 67
“Last, we wanted to attempt to correct our association results for any possible population stratification in a genomic control type of approach [e.g., Devlin and Roeder, 1999 ].”
Association study of the serotonin transporter gene polymorphism in obsessive–compulsive disorder
Camarena, B., Rinetti, G., Cruz, C., Hernández, S., Fuente, J. R. D. L., & Nicolini, H. (2001) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145701002516 · Cited by 66
“Many association studies have resulted in controversial results because population stratification cannot easily be avoided (Devlin and Roeder, 1999).”
BackgroundFaST-LMM-Select for addressing confounding from spatial structure and rare variants
Listgarten, J., Lippert, C., & Heckerman, D. E. (2013) · Nature Genetics · doi:10.1038/ng.2620 · Cited by 66
Li, M., Tiirikka, T., & Kantanen, J. (2013) · Heredity · doi:10.1038/hdy.2013.83 · Cited by 66
Matullo, G., Guarrera, S., Betti, M., Fiorito, G., Ferrante, D., Voglino, F., Cadby, G., Gaetano, C. D., Rosa, F., RUSSO, A. E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061253 · Cited by 64
“The effective removal of any population structure bias was checked by the l-inflation factor parameter [59] (Figure S2).”
MethodImproving the Power of GWAS and Avoiding Confounding from Population Stratification with PC-Select
Tucker, G., Price, A. L., & Berger, B. (2014) · Genetics · doi:10.1534/genetics.114.164285 · Cited by 64
“We generated 500 candidate test null SNPs that were not causal, and to measure in fl ation we calculated l GC , the median Wald statistic on these SNPs divided by the theoretical median under the null distribution (Devlin and Roeder 1999).”
Schork, A. J., Wang, Y., Thompson, W. K., Dale, A. M., & Andreassen, O. A. (2015) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.10.008 · Cited by 64
“Traditionally, genome-wide ‘enrichment’ of this type was attributed to statistical artifacts from poor study design (population stratification or cryptic relatedness) [24], in part because GWAS were initially predicted to uncover relatively few loci of moderate effect.”
BackgroundNolte, I. M., Wallace, C., Newhouse, S., Waggott, D. M., Fu, J., Soranzo, N., Gwilliam, R., Deloukas, P., Savelieva, I., Zheng, D., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006138 · Cited by 66
“Possible bias caused by population stratification was checked by calculating the genomic inflation factor l of the metaanalysis [27,28].”
MethodGenome-wide association study of lung function phenotypes in a founder population
Yao, T., Du, G., Han, L., Sun, Y., Hu, D., Yang, J. J., Mathias, R. A., Roth, L. A., Rafaels, N. M., Thompson, E. E., et al. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.06.018 · Cited by 65
“The GWAS P values for FEV1 and FVC were adjusted by using their genomic control.(45) The Bonferroni-corrected genome-wide significance threshold was P < 2.”
MethodProkopenko, D., Hecker, J., Silverman, E. K., Pagano, M., Nöthen, M. M., Dina, C., Lange, C., & Fier, H. L. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv752 · Cited by 62
Genome-Wide Association Study of Susceptibility Loci for Radiation-Induced Brain Injury
Wang, T., Shen, G., Chen, M., Zhang, J., Sun, Y. H., He, J., Xue, W., Li, X., Huang, S., Zheng, X., et al. (2018) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djy150 · Cited by 65
“A quantile–quantile plot was used to evaluate the overall statistical significance of the GWAS and the deviation of observed vs expected distribution of P values was represented by inflation factor (kGC) (25).”
MethodCorrection of Population Stratification in Large Multi-Ethnic Association Studies
Serre, D., Montpetit, A., Paré, G., Engert, J. C., Yusuf, S., Keavney, B. D., Hudson, T. J., & Anand, S. S. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001382 · Cited by 64
“Devlin and Roeder [14] proposed to use random SNPs as ‘‘genomic controls’’ to estimate the average effect of population substructure in the sample and then correct the test statistics accordingly.”
BackgroundAssociation of the HSPG2 Gene with Neuroleptic-Induced Tardive Dyskinesia
Syu, A., Ishiguro, H., Inada, T., Horiuchi, Y., Tanaka, S., Ishikawa, M., Arai, M., Itokawa, M., Niizato, K., Iritani, S., et al. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.220 · Cited by 64
“The potential impact of population structure on this association study was evaluated by using the genome-wide w inflation factor, l, as a genomic control (Devlin and Roeder, 1999; Devlin et al, 2001).”
MethodHu, Z., Zhang, D., Zhang, G., Kan, G., Hong, D., & Yu, D. (2014) · Ikushugaku zasshi · doi:10.1270/jsbbs.63.441 · Cited by 64
Association Between the Catechol-O-Methyltransferase Val158Met Polymorphism and Cocaine Dependence
Lohoff, F. W., Weller, A. E., Bloch, P. J., Nall, A. H., Ferraro, T. N., Kampman, K. M., Pettinati, H. M., Oslin, D. W., Dackis, C. A., O’Brien, C. P., et al. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.126 · Cited by 64
“Possible strategies to control for these stratification issues are the use of genomic controls (Bacanu et al, 2000; Devlin and Roeder, 1999) and/ or the use of a family-based association design, a strategy that matches the genotype of an affected offspring with parental alleles not inherited by the offspring (Spielman…”
MethodGenetic modifiers of Mendelian disease: Huntington’s disease and the trinucleotide repeat disorders
Holmans, P., Massey, T. H., & Jones, L. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx261 · Cited by 69
“The degree of inflation can be quantified by the genomic inflation factor (cid:1), defined as the median of the observed test statistics divided by its expected value (39).”
BackgroundChapter 1 Common Genetic Variation and Human Disease
Orr, N., & Chanock, S. J. (2008) · Advances in genetics · doi:10.1016/s0065-2660(08)00601-9 · Cited by 66
Talkowski, M. E., Mansour, H., Chowdari, K. V., Wood, J. A., Butler, A., Varma, P. G., Prasad, S., Semwal, P., Triptish Bhatia, A., Deshpande, S. N., et al. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.04.012 · Cited by 64
Self-citationMargres, M. J., Jones, M. E., Epstein, B., Kerlin, D. H., Comte, S., Fox, S., Fraik, A. K., Hendricks, S. A., Huxtable, S. J., Lachish, S., et al. (2018) · Molecular Ecology · doi:10.1111/mec.14853 · Cited by 63
“The genomic inflation factor is the ratio between the median Z‐scores and the expected median Z‐ scores for a χ2 distribution with one degree of freedom (Devlin & Roeder, 1999), and works under the assumption that most SNPs are not strongly associated with the phenotype of interest.”
BackgroundHow rare and common risk variation jointly affect liability for autism spectrum disorder
Klei, L., McClain, L. L., Mahjani, B., Panayidou, K., Rubeis, S. D., Grahnat, A.-C. S., Karlsson, G., Lu, Y., Melhem, N., Xu, X., et al. (2021) · Molecular Autism · doi:10.1186/s13229-021-00466-2 · Cited by 65
Self-citationAssociation of SSR markers with functional traits from heat stress in diverse tall fescue accessions
Sun, X., Du, Z., Ren, J., Amombo, E., Hu, T., & Fu, J. (2015) · BMC Plant Biology · doi:10.1186/s12870-015-0494-5 · Cited by 63
“So in view of the geographical origins, local adaptation, and breeding history of genotypes in association mapping panel, the nonindependent samples would often encompass both population structure and familiar relatedness [35,36].”
BackgroundGene Expression and Genetic Variation Data Implicate PCLO in Bipolar Disorder
Choi, K. H., Higgs, B. W., Wendland, J. R., Song, J. C., McMahon, F. J., & Webster, M. J. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.042 · Cited by 65
IL10 Haplotype Associated with Tuberculin Skin Test Response but Not with Pulmonary TB
Thye, T., Browne, E. N. L., Chinbuah, M. A., Gyapong, J. O., Osei, I., Owusu‐Dabo, E., Brattig, N. W., Niemann, S., Rüsch–Gerdes, S., Horstmann, R. D., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005420 · Cited by 63
“To assess whether population stratification was a major concern in our study, the median of the Armitage’s trend test statistics of 61 unlinked biallelic markers (see Supplementary Table S1) was analysed to estimate the inflation factor l for genomic control [29].”
MethodRosenberg, N. A., & Nordborg, M. (2006) · Genetics · doi:10.1534/genetics.105.055335 · Cited by 61
Bouaziz, M., Ambroise, C., & Guedj, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028845 · Cited by 63
“Several main approaches exist to account for population stratification in GWAS: Genomic Control [9] [10], Principal Component Analysis (PCA) based methods [11] [12], Regression models [4] [13], and Meta-Analyses.”
MethodLarge‐Scale Candidate Gene Analysis of Spontaneous Clearance of Hepatitis C Virus
Mosbruger, T. L., Duggal, P., Goedert, J. J., Kirk, G. D., Hoots, W. K., Tobler, L. H., Busch, M. P., Peters, M. G., Rosen, H. R., Thomas, D. L., et al. (2010) · The Journal of Infectious Diseases · doi:10.1086/651606 · Cited by 63
“We used the genomic control (GC) [16] procedure to correct for population stratification.”
MethodJia, G., Ping, J., Guo, X., Yang, Y., Tao, R., Li, B., Ambs, S., Barnard, M. E., Chen, Y., García‐Closas, M., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01736-4 · Cited by 62
Shirts, B. H., Wood, J. A., Yolken, R. H., & Nimgaonkar, V. L. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.06.037 · Cited by 63
Lee, K., Byun, M.-J., Kang, K.-S., Park, E.-W., Lee, S. H., Cho, S., Kim, H.-Y., Kim, K.-W., Lee, T., Park, J., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016356 · Cited by 62
“The p-values were adjusted by a genomic control method [40] and followed by FDR [41] corrections as implemented in PLINK [59].”
MethodResultThe GABA transporter 1 (SLC6A1): a novel candidate gene for anxiety disorders
Thoeringer, C. K., Ripke, S., Unschuld, P. G., Lucae, S., Ising, M., Bettecken, T., Uhr, M., Keck, M. E., Mueller-Myhsok, B., Holsboer, F., et al. (2008) · Journal of Neural Transmission · doi:10.1007/s00702-008-0075-y · Cited by 67
“To test for the effects of population stratification, we applied the method of genomic controls (Binder et al. 2004; Devlin and Roeder 1999) for the data obtained from”
Guo, S. (2005) · Molecular Human Reproduction · doi:10.1093/molehr/gah206 · Cited by 62
“Fourth, special attention needs to be paid to select proper controls (see Holt and Weiss, 2000) and for controlling for population heterogeneity, such as using genomic control (Devlin and Roeder, 1999).”
BackgroundNQO1 Polymorphisms and De Novo Childhood Leukemia: A HuGE Review and Meta-Analysis
Guha, N., Chang, J. S.-M., Chokkalingam, A. P., Wiemels, J. L., Smith, M. T., & Buffler, P. A. (2008) · American Journal of Epidemiology · doi:10.1093/aje/kwn246 · Cited by 62
Thornton, T. A., & Bermejo, J. L. (2014) · Genetic Epidemiology · doi:10.1002/gepi.21819 · Cited by 60
“The genomic control inflation factor [Devlin and Roeder, 1999] λ was 1.”
BackgroundInfluentialPedroso, I., Lourdusamy, A., Rietschel, M., Nöthen, M. M., Cichon, S., McGuffin, P., Al-Chalabi, A., Barnes, M. R., & Breen, G. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.12.031 · Cited by 59
Metadata
- Authors
- Devlin, B., & Roeder, K.
- Affiliations
- University of Pittsburgh (US)
- Carnegie Mellon University (US)
- Corresponding author
- Devlin, B.
- Roeder, Kathryn
- Venue
- Biometrics
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-12
- Volume
- 55
- Issue
- 4
- Pages
- 997-1004
- ISSN
- 0006-341X (ISSN-L)
- 1541-0420
- OpenAlex
- W2008047653
- Cited by
- 3,162
- References
- 34
- Citations by year
- 2026: 86 · 2025: 79 · 2024: 87 · 2023: 84 · 2022: 115 · 2021: 102 · 2020: 94 · 2019: 118 · 2018: 128 · 2017: 124 · 2016: 137 · 2015: 170 · 2014: 143 · 2013: 175 · 2012: 172
- FWCI
- 14.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biometrics (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- University of Pittsburgh
- National Institutes of Health
- National Institute of Mental Health (NIMH 57881, P01MH056193, R01MH057881, NIMH 56193)
- 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
- genomic control, association studies, single nucleotide polymorphisms, case-control data, population heterogeneity, multiple testing correction, false positives, complex diseases, model assumption violation
- MeSH terms
- Bayes Theorem, Biometry, Genetic Techniques, Humans, Models, Genetic, Models, Statistical, Genome, Human, Case-Control Studies
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