A Powerful and Flexible Multilocus Association Test for Quantitative Traits
Open accessAbstract
Association mapping of complex traits typically employs tagSNP genotype data to identify a trait locus within a region of interest. However, considerable debate exists regarding the most powerful strategy for utilizing such tagSNP data for inference. A popular approach tests each tagSNP within the region individually, but such tests could lose power as a result of incomplete linkage disequilibrium between the genotyped tagSNP and the trait locus. Alternatively, one can jointly test all tagSNPs simultaneously within the region (by using genotypes or haplotypes), but such multivariate tests have large degrees of freedom that can also compromise power. Here, we consider a semiparametric model for quantitative-trait mapping that uses genetic information from multiple tagSNPs simultaneously in analysis but produces a test statistic with reduced degrees of freedom compared to existing multivariate approaches. We fit this model by using a dimension-reducing technique called least-squares kernel machines, which we show is identical to analysis using a specific linear mixed model (which we can fit by using standard software packages like SAS and R). Using simulated SNP data based on real data from the International HapMap Project, we demonstrate that our approach often has superior performance for association mapping of quantitative traits compared to the popular approach of single-tagSNP testing. Our approach is also flexible, because it allows easy modeling of covariates and, if interest exists, high-dimensional interactions among tagSNPs and environmental predictors.
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?
Ridge regression and LASSO have been considered in genetic association analysis contexts, and other methods have been proposed.
“Two such techniques, ridge regression74 and the LASSO75,76 have been considered in genetic association analysis contexts, and other methods have also been proposed as well.77–80, 81”
From Statistical analysis strategies for association studies involving rare variants (2010) · cites this paper as [80]
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
An Introduction to Support Vector Machines and Other Kernel-based Learning Methods
Cristianini, N., & Shawe-Taylor, J. (2000) · doi:10.1017/cbo9780511801389 · Cited by 13,855 · see citing works
Gaussian Processes for Machine Learning
Rasmussen, C. E., & Williams, C. K. I. (2005) · doi:10.7551/mitpress/3206.001.0001 · Cited by 11,705 · see citing works
A New Statistical Method for Haplotype Reconstruction from Population Data
Stephens, M., Smith, N. J. C., & Donnelly, P. (2001) · The American Journal of Human Genetics · doi:10.1086/319501 · Cited by 7,460 · 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
An Introduction to Support Vector Machines and Other Kernel‐based Learning Methods
(2001) · Kybernetes · doi:10.1108/k.2001.30.1.103.6 · Cited by 3,358 · see citing works
Multipoint Quantitative-Trait Linkage Analysis in General Pedigrees
Almasy, L. A., & Blangero, J. (1998) · The American Journal of Human Genetics · doi:10.1086/301844 · Cited by 3,007 · 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
Scheet, P. A., & Stephens, M. (2006) · The American Journal of Human Genetics · doi:10.1086/502802 · Cited by 1,949 · see citing works
Score Tests for Association between Traits and Haplotypes when Linkage Phase Is Ambiguous
Schaid, D. J., Rowland, C. M., Tines, D. E., Jacobson, R. M., & Poland, G. A. (2002) · The American Journal of Human Genetics · doi:10.1086/338688 · Cited by 1,772 · see citing works
Nyholt, D. R. (2004) · The American Journal of Human Genetics · doi:10.1086/383251 · Cited by 1,699 · see citing works
Efficiency and power in genetic association studies
de Bakker, P. I. W., Yelensky, R., Pe’er, I., Gabriel, S., Daly, M. J., & Altshuler, D. (2005) · Nature Genetics · doi:10.1038/ng1669 · Cited by 1,678 · see citing works
Carlson, C. S., Eberle, M. A., Rieder, M. J., Qian, Y., Kruglyak, L., & Nickerson, D. A. (2004) · The American Journal of Human Genetics · doi:10.1086/381000 · Cited by 1,578 · see citing works
Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix
Li, J., & Ji, L. (2005) · Heredity · doi:10.1038/sj.hdy.6800717 · Cited by 1,458 · see citing works
Accounting for Decay of Linkage Disequilibrium in Haplotype Inference and Missing-Data Imputation
Stephens, M., & Scheet, P. A. (2005) · The American Journal of Human Genetics · doi:10.1086/428594 · Cited by 1,337 · see citing works
A General Test of Association for Quantitative Traits in Nuclear Families
Abecasis, G. R., Cardon, L. R., & Cookson, W. O. C. (2000) · The American Journal of Human Genetics · doi:10.1086/302698 · Cited by 1,126 · see citing works
Zaykin, D. V., Westfall, P. H., Young, S. S., Karnoub, M. A., Wagner, M. J., & Ehm, M. G. (2002) · Human Heredity · doi:10.1159/000057986 · Cited by 655 · see citing works
Ryan, T. P. (2004) · Journal of Quality Technology · doi:10.1080/00224065.2004.11980270 · Cited by 587 · see citing works
Robust variance-components approach for assessing genetic linkage in pedigrees.
Amos, C. I. (1994) · PubMed · Cited by 520 · see citing works
Truncated product method for combining P ‐values
Zaykin, D. V., Анатольевич, Ж. Л., Westfall, P. H., & Weir, B. S. (2002) · Genetic Epidemiology · doi:10.1002/gepi.0042 · Cited by 508 · see citing works
Bias Correction in Generalised Linear Mixed Models with a Single Component of Dispersion
Breslow, N. E., & LIN, X. (1995) · Biometrika · doi:10.1093/biomet/82.1.81 · Cited by 494 · see citing works
Self-citationSo Many Correlated Tests, So Little Time! Rapid Adjustment of P Values for Multiple Correlated Tests
Conneely, K. N., & Boehnke, M. (2007) · The American Journal of Human Genetics · doi:10.1086/522036 · Cited by 446 · see citing works
Chapman, J. M., Cooper, J. D., Todd, J. A., & Clayton, D. G. (2003) · Human Heredity · doi:10.1159/000073729 · Cited by 414 · see citing works
Bias Correction in Generalized Linear Mixed Models With Multiple Components of Dispersion
Lin, X., & Breslow, N. E. (1996) · Journal of the American Statistical Association · doi:10.1080/01621459.1996.10476971 · Cited by 408 · see citing works
Self-citationA Comparison of Phasing Algorithms for Trios and Unrelated Individuals
Marchini, J., Cutler, D., Patterson, N., Stephens, M., Eskin, E., Halperin, E., Lin, S., Qin, Z. S., Munro, H. M., Abecasis, G. R., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/500808 · Cited by 341 · see citing works
Liu, D., Lin, X., & Ghosh, D. (2007) · Biometrics · doi:10.1111/j.1541-0420.2007.00799.x · Cited by 332 · see citing works
Self-citationAllison, D. B., Neale, M. C., Zannolli, R., Schork, N. J., Amos, C. I., & Blangero, J. (1999) · The American Journal of Human Genetics · doi:10.1086/302487 · Cited by 297 · see citing works
Testing association between disease and multiple SNPs in a candidate gene
Gauderman, W. J., Murcray, C. E., Gilliland, F. D., & Conti, D. V. (2007) · Genetic Epidemiology · doi:10.1002/gepi.20219 · Cited by 199 · see citing works
Tag SNP selection for association studies
Stram, D. O. (2004) · Genetic Epidemiology · doi:10.1002/gepi.20028 · Cited by 191 · see citing works
Generalized Genomic Distance–Based Regression Methodology for Multilocus Association Analysis
Wessel, J., & Schork, N. J. (2006) · The American Journal of Human Genetics · doi:10.1086/508346 · Cited by 190 · see citing works
Linkage Disequilibrium Mapping via Cladistic Analysis of Single-Nucleotide Polymorphism Haplotypes
Durrant, C., Zondervan, K. T., Cardon, L. R., Hunt, S. E., Deloukas, P., & Morris, A. P. (2004) · The American Journal of Human Genetics · doi:10.1086/422174 · Cited by 186 · see citing works
Testing Untyped Alleles (TUNA)—applications to genome‐wide association studies
Nicolae, D. L. (2006) · Genetic Epidemiology · doi:10.1002/gepi.20182 · Cited by 185 · see citing works
An efficient Monte Carlo approach to assessing statistical significance in genomic studies
Lin, D. Y. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bti053 · Cited by 180 · see citing works
Multilevel Modeling in Epidemiology with GLIMMIX
Witte, J. S., Greenland, S., Kim, L.-L., & Arab, L. (2000) · Epidemiology · doi:10.1097/00001648-200011000-00012 · Cited by 139 · see citing works
Hypothesis testing in semiparametric additive mixed models
Zhang, D. (2003) · Biostatistics · doi:10.1093/biostatistics/4.1.57 · Cited by 136 · see citing works
Nonparametric Tests of Association of Multiple Genes with Human Disease
Schaid, D. J., McDonnell, S. K., Hebbring, S. J., Cunningham, J. M., & Thibodeau, S. N. (2005) · The American Journal of Human Genetics · doi:10.1086/429838 · Cited by 135 · see citing works
Improved Power by Use of a Weighted Score Test for Linkage Disequilibrium Mapping
Wang, T., & Elston, R. C. (2007) · The American Journal of Human Genetics · doi:10.1086/511312 · Cited by 117 · see citing works
Analysis of single‐locus tests to detect gene/disease associations
Roeder, K., Bacanu, S., Sonpar, V. A., Zhang, X. D., & Devlin, B. (2005) · Genetic Epidemiology · doi:10.1002/gepi.20050 · Cited by 97 · see citing works
Valle, T. T., Tuomilehto, J., Bergman, R. N., Ghosh, S., Hauser, E. R., Eriksson, J. G., Nylund, S. J., Kohtamäki, K., Toivanen, L., Vidgrén, G., et al. (1998) · Diabetes Care · doi:10.2337/diacare.21.6.949 · Cited by 90 · see citing works
Genome Association Studies of Complex Diseases by Case-Control Designs
Fan, R., & Knapp, M. (2003) · The American Journal of Human Genetics · doi:10.1086/373966 · Cited by 80 · see citing works
Regression-Based Association Analysis with Clustered Haplotypes through Use of Genotypes
Tzeng, J., Wang, C., Kao, J., & Hsiao, C. K. (2006) · The American Journal of Human Genetics · doi:10.1086/500025 · Cited by 79 · see citing works
Enriching the Analysis of Genomewide Association Studies with Hierarchical Modeling
Chen, G. K., & Witte, J. S. (2007) · The American Journal of Human Genetics · doi:10.1086/519794 · Cited by 79 · see citing works
Hung, R. J., Brennan, P., MALAVEILLE, C., Porru, S., Donato, F., Boffetta, P., & Witte, J. S. (2004) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.1013.13.6 · Cited by 78 · see citing works
Haplotype-Based Association Analysis via Variance-Components Score Test
Tzeng, J., & Zhang, D. (2007) · The American Journal of Human Genetics · doi:10.1086/521558 · Cited by 71 · see citing works
Hierarchical Modeling of Linkage Disequilibrum: Genetic Structure and Spatial Relations
Conti, D. V., & Witte, J. S. (2003) · The American Journal of Human Genetics · doi:10.1086/346117 · Cited by 68 · see citing works
Leveraging the HapMap Correlation Structure in Association Studies
Zaitlen, N., Kang, H. M., Eskin, E., & Halperin, E. (2007) · The American Journal of Human Genetics · doi:10.1086/513109 · Cited by 59 · see citing works
Multiple hypothesis testing strategies for genetic case–control association studies
Rosenberg, P. S., Che, A., & Chen, B. E. (2005) · Statistics in Medicine · doi:10.1002/sim.2407 · Cited by 43 · see citing works
Genetic analysis with hierarchical models
Witte, J. S. (1997) · Genetic Epidemiology · doi:10.1002/(sici)1098-2272(1997)14:6 · Cited by 33 · see citing works
Flagged first, then by citations
2 of the 49 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Rare-Variant Association Testing for Sequencing Data with the Sequence Kernel Association Test
Wu, M. C., Lee, S., Cai, T., Li, Y., Boehnke, M., & Lin, X. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.05.029 · Cited by 2,317 · see citing works
Self-citationAnalysing biological pathways in genome-wide association studies
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2884 · Cited by 757 · see citing works
Powerful SNP-Set Analysis for Case-Control Genome-wide Association Studies
Wu, M. C., Kraft, P., Epstein, M. P., Taylor, D. M., Chanock, S. J., Hunter, D. J., & Lin, X. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.05.002 · Cited by 589 · see citing works
Self-citationStatistical analysis strategies for association studies involving rare variants
Bansal, V., Libiger, O., Torkamani, A., & Schork, N. J. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2867 · Cited by 455 · see citing works
Zhao, N., Chen, J., Carroll, I. M., Ringel-Kulka, T., Epstein, M. P., Zhou, H., Zhou, J. J., Ringel, Y., Li, H., & Wu, M. C. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.04.003 · Cited by 306 · see citing works
Self-citationGenetic mapping of quantitative trait loci in crops
XU, Y. C., Li, P., Yang, Z., & Xu, C. (2016) · The Crop Journal · doi:10.1016/j.cj.2016.06.003 · Cited by 283 · see citing works
Pathway analysis by adaptive combination of P‐values
Yu, K. F., Li, Q., Bergen, A. W., Pfeiffer, R. M., Rosenberg, P. S., Caporaso, N. E., Kraft, P., & Chatterjee, N. (2009) · Genetic Epidemiology · doi:10.1002/gepi.20422 · Cited by 267 · see citing works
Comparison of statistical tests for disease association with rare variants
Basu, S., & Pan, W. (2011) · Genetic Epidemiology · doi:10.1002/gepi.20609 · Cited by 215 · see citing works
Sequence Kernel Association Test for Quantitative Traits in Family Samples
Chen, H., Meigs, J. B., & Dupuis, J. (2012) · Genetic Epidemiology · doi:10.1002/gepi.21703 · Cited by 212 · see citing works
Vounou, M., Nichols, T. E., & Montana, G. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.07.002 · Cited by 209 · see citing works
Kernel-based whole-genome prediction of complex traits: a review
Morota, G., & Gianola, D. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00363 · Cited by 162 · see citing works
Gene set analysis of SNP data: benefits, challenges, and future directions
Fridley, B. L., & Biernacka, J. M. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2011.57 · Cited by 138 · see citing works
HPA axis genetic variation, cortisol and psychosis in major depression
Schatzberg, A. F., Keller, J., Tennakoon, L., Lembke, A., Williams, G., Kraemer, F. B., Sarginson, J. E., Lazzeroni, L. C., & Murphy, G. M. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.129 · Cited by 131 · see citing works
Ghosh, A., Murugesan, G., Chen, K., Zhang, L., Wang, Q. K., Febbraio, M., Anselmo, R. M., Marchant, K., Barnard, J., & Silverstein, R. L. (2011) · Blood · doi:10.1182/blood-2011-02-338582 · Cited by 130 · see citing works
Unsupervised multiple kernel learning for heterogeneous data integration
Mariette, J., & Vialaneix, N. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx682 · Cited by 120 · see citing works
SNP Set Association Analysis for Familial Data
Schifano, E. D., Epstein, M. P., Bielak, L. F., Jhun, M. A., Kardia, S. L. R., Peyser, P. A., & Lin, X. (2012) · Genetic Epidemiology · doi:10.1002/gepi.21676 · Cited by 107 · see citing works
Self-citationZeng, P., Shao, Z., & Zhou, X. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.05.042 · Cited by 97 · see citing works
Schaid, D. J. (2010) · Human Heredity · doi:10.1159/000312641 · Cited by 93 · see citing works
Schaid, D. J., McDonnell, S. K., Sinnwell, J. P., & Thibodeau, S. N. (2013) · Genetic Epidemiology · doi:10.1002/gepi.21727 · Cited by 92 · see citing works
Joint analysis of SNP and gene expression data in genetic association studies of complex diseases
Huang, Y.-T., VanderWeele, T. J., & Lin, X. (2014) · The Annals of Applied Statistics · doi:10.1214/13-aoas690 · Cited by 88 · see citing works
Self-citationMultivariate Phenotype Association Analysis by Marker‐Set Kernel Machine Regression
Maity, A., Sullivan, P. F., & Tzeng, J. (2012) · Genetic Epidemiology · doi:10.1002/gepi.21663 · Cited by 87 · see citing works
Ge, T., Feng, J., Hibar, D. P., Thompson, P. M., & Nichols, T. E. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.07.012 · Cited by 89 · see citing works
DASH: A Method for Identical-by-Descent Haplotype Mapping Uncovers Association with Recent Variation
Gusev, A., Kenny, E. E., Lowe, J. K., Salit, J., Saxena, R., Kathiresan, S., Altshuler, D., Friedman, J. M., Breslow, J. L., & Pe’er, I. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.04.023 · Cited by 86 · see citing works
Gene-Based Testing of Interactions in Association Studies of Quantitative Traits
Ma, L., Clark, A. G., & Keinan, A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003321 · Cited by 83 · see citing works
JOINT ANALYSIS OF SNP AND GENE EXPRESSION DATA IN GENETIC ASSOCIATION STUDIES OF COMPLEX DISEASES1Preprint
Huang, Y., Tyler, J., V, & Lin, X. (2013) · Cited by 88 · see citing works
Self-citationLocke, A. E., Dooley, K. J., Tinker, S. W., Cheong, S. Y., Feingold, E., Allen, E. G., Freeman, S. B., Torfs, C. P., Cua, C. L., Epstein, M. P., et al. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20518 · Cited by 84 · see citing works
Self-citationMachiela, M. J., Lindström, S., Allen, N. E., Haiman, C. A., Albanes, D., Barricarte, A., Berndt, S. I., Bueno-de-Mesquita, H. B., Chanock, S. J., Gaziano, J. M., et al. (2012) · American Journal of Epidemiology · doi:10.1093/aje/kws191 · Cited by 81 · see citing works
Association tests using kernel‐based measures of multi‐locus genotype similarity between individuals
Mukhopadhyay, I., Feingold, E., Weeks, D. E., & Thalamuthu, A. (2009) · Genetic Epidemiology · doi:10.1002/gepi.20451 · Cited by 79 · see citing works
Functional Linear Models for Association Analysis of Quantitative Traits
Fan, R., Wang, Y., Mills, J. L., Wilson, A. F., Wilson, J., & Xiong, M. (2013) · Genetic Epidemiology · doi:10.1002/gepi.21757 · Cited by 76 · see citing works
Tzeng, J., Zhang, D., Pongpanich, M., Smith, C., McCarthy, M. I., Sale, M. M., Worrall, B. B., Hsu, F., Thomas, D. C., & Sullivan, P. F. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.07.007 · Cited by 79 · see citing works
A Statistical Approach for Testing Cross-Phenotype Effects of Rare Variants
Broadaway, K. A., Cutler, D. J., Duncan, R., Moore, J. L., Ware, E. B., Jhun, M. A., Bielak, L. F., Zhao, W., Smith, J. A., Peyser, P. A., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.01.017 · Cited by 78 · see citing works
Self-citationPan, W. (2011) · Genetic Epidemiology · doi:10.1002/gepi.20567 · Cited by 71 · see citing works
Kernel Machine SNP‐Set Testing Under Multiple Candidate Kernels
Wu, M. C., Maity, A., Lee, S., Simmons, E., Harmon, Q. E., Lin, X., Engel, S. M., Molldrem, J. J., & Armistead, P. M. (2013) · Genetic Epidemiology · doi:10.1002/gepi.21715 · Cited by 75 · see citing works
Self-citationBallard, D. H., Cho, J. H., & Zhao, H. (2009) · Genetic Epidemiology · doi:10.1002/gepi.20448 · Cited by 74 · see citing works
Massively expedited genome-wide heritability analysis (MEGHA)
Ge, T., Nichols, T. E., Lee, P. H., Holmes, A. J., Roffman, J. L., Buckner, R. L., Sabuncu, M. R., & Smoller, J. W. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415603112 · Cited by 69 · see citing works
Desrivières, S., Lourdusamy, A., Tao, C., Toro, R., Jia, T., Loth, E., Medina, L. M., Kepa, A., Fernandes, A. R., Ruggeri, B., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.197 · Cited by 69 · see citing works
Sterken, R., Kiekens, R., Boruc, J., Zhang, F., Vercauteren, A., Vercauteren, I., Smet, L. D., Dhondt, S., Inzé, D., Veylder, L. D., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120811109 · Cited by 67 · see citing works
Tang, S., Buchman, A. S., Jager, P. L. D., Bennett, D. A., Epstein, M. P., & Yang, J. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009482 · Cited by 64 · see citing works
Self-citationKernel machine SNP-set analysis for censored survival outcomes in genome-wide association studies
Lin, X., Cai, T., Wu, M. C., Zhou, Q., Liu, G., Christiani, D. C., & Lin, X. (2011) · Genetic Epidemiology · doi:10.1002/gepi.20610 · Cited by 62 · see citing works
Self-citationCigarette smoking increases copy number alterations in nonsmall-cell lung cancer
Huang, Y., Lin, X., Liu, Y., Chirieac, L. R., McGovern, R., Wain, J. R., Heist, R. S., Skaug, V., Zienolddiny, S., Haugen, A., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102769108 · Cited by 60 · see citing works
Self-citationA Powerful Pathway-Based Adaptive Test for Genetic Association with Common or Rare Variants
Pan, W., Kwak, I., & Wei, P. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.05.018 · Cited by 58 · see citing works
Predicting Genetic Values: A Kernel-Based Best Linear Unbiased Prediction With Genomic Data
Ober, U., Erbe, M., Long, N., Porcu, E., Schlather, M., & Simianer, H. (2011) · Genetics · doi:10.1534/genetics.111.128694 · Cited by 57 · see citing works
Robust linear regression methods in association studies
Lourenço, V., Pires, A. M., & Kirst, M. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr006 · Cited by 56 · see citing works
Gene-centric gene–gene interaction: a model-based kernel machine method
Li, S., & Cui, Y. (2012) · The Annals of Applied Statistics · doi:10.1214/12-aoas545 · Cited by 51 · see citing works
An Evolutionary Framework for Association Testing in Resequencing Studies
King, C. R., Rathouz, P. J., & Nicolae, D. L. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001202 · Cited by 53 · see citing works
Kernel methods for large-scale genomic data analysis
Wang, X., Xing, E. P., & Schaid, D. J. (2014) · Briefings in Bioinformatics · doi:10.1093/bib/bbu024 · Cited by 50 · see citing works
A Large-scale genetic association study of esophageal adenocarcinoma risk
Liu, C.-Y., Wu, M. C., Chen, F., Ter‐Minassian, M., Asomaning, K., Zhai, R., Wang, Z., Su, L., Heist, R. S., Kulke, M. H., et al. (2010) · Carcinogenesis · doi:10.1093/carcin/bgq092 · Cited by 50 · see citing works
Self-citationQu, L., Guennel, T., & Marshall, S. L. (2013) · Biometrics · doi:10.1111/biom.12095 · Cited by 49 · see citing works
Small Sample Kernel Association Tests for Human Genetic and Microbiome Association Studies
Chen, J., Chen, W., Zhao, N., Wu, M. C., & Schaid, D. J. (2015) · Genetic Epidemiology · doi:10.1002/gepi.21934 · Cited by 47 · see citing works
Zhan, X., Zhao, N., Plantinga, A., Thornton, T. A., Conneely, K. N., Epstein, M. P., & Wu, M. C. (2017) · Genetics · doi:10.1534/genetics.116.199646 · Cited by 48 · see citing works
Self-citationA Guide to Illumina BeadChip Data Analysis
Wu, M. C., & Kuan, P. F. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7481-8_16 · Cited by 47 · see citing works
SBERIA: Set‐Based Gene‐Environment Interaction Test for Rare and Common Variants in Complex Diseases
Jiao, S., Hsu, L., Bezieau, S., Brenner, H., Chan, A. T., Chang-Claude, J. C., Marchand, L. L., Lemire, M., Newcomb, P. A., Slattery, M. L., et al. (2013) · Genetic Epidemiology · doi:10.1002/gepi.21735 · Cited by 43 · see citing works
Genome-Wide Meta-Analysis of Myopia and Hyperopia Provides Evidence for Replication of 11 Loci
Simpson, C. L., Wojciechowski, R., Oexle, K., Murgia, F., Portas, L., Li, X., Verhoeven, V. J. M., Vitart, V., Schäche, M., Hosseini, S. M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107110 · Cited by 43 · see citing works
Edwards, A. O., Fridley, B. L., James, K. M., Sharma, A. K., Cunningham, J. M., & Tosakulwong, N. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003813 · Cited by 43 · see citing works
Huang, Y., Liang, L., Moffatt, M. F., Cookson, W., & Lin, X. (2015) · Genetic Epidemiology · doi:10.1002/gepi.21905 · Cited by 39 · see citing works
Self-citationZhang, Y., Guan, W., & Pan, W. (2012) · Genetic Epidemiology · doi:10.1002/gepi.21691 · Cited by 38 · see citing works
Performance of a blockwise approach in variable selection using linkage disequilibrium information
Dehman, A., Ambroise, C., & Neuvial, P. (2015) · BMC Bioinformatics · doi:10.1186/s12859-015-0556-6 · Cited by 36 · see citing works
Gong, X., Lu, W., Kendrick, K. M., Pu, W., Wang, C., Li, J., Lu, G., Liu, Z., Liu, H., & Feng, J. (2014) · Human Brain Mapping · doi:10.1002/hbm.22560 · Cited by 35 · see citing works
U‐Statistics‐based Tests for Multiple Genes in Genetic Association Studies
Wei, Z., Li, M., Rebbeck, T. R., & Li, H. (2008) · Annals of Human Genetics · doi:10.1111/j.1469-1809.2008.00473.x · Cited by 35 · see citing works
Zou, F., Huang, H., Lee, S., & Hoeschele, I. (2010) · Genetics · doi:10.1534/genetics.109.113688 · Cited by 35 · see citing works
Lindström, S., Hunter, D. J., Grönberg, H., Stattin, P. E., Wiklund, F. E., Xu, J., Chanock, S. J., Hayes, R. B., & Kraft, P. (2010) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-09-0618 · Cited by 33 · see citing works
Hua, W., & Ghosh, D. (2015) · Biometrics · doi:10.1111/biom.12314 · Cited by 31 · see citing works
Self-citationRegion-Based Association Analysis of Human Quantitative Traits in Related Individuals
Belonogova, N. M., Svishcheva, G. R., van Duijn, C. M., Aulchenko, Y. S., & Axenovich, T. I. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065395 · Cited by 30 · see citing works
A review of kernel methods for genetic association studies
Larson, N. B., Chen, J., & Schaid, D. J. (2019) · Genetic Epidemiology · doi:10.1002/gepi.22180 · Cited by 30 · see citing works
Generalized Functional Linear Models for Gene‐Based Case‐Control Association Studies
Fan, R., Wang, Y., Mills, J. L., Carter, T. C., Lobach, I. V., Wilson, A. F., Wilson, J., Weeks, D. E., & Xiong, M. (2014) · Genetic Epidemiology · doi:10.1002/gepi.21840 · Cited by 30 · see citing works
Daye, Z. J., Li, H., & Wei, Z. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks024 · Cited by 30 · see citing works
Ge, T., Nichols, T. E., Ghosh, D., Mormino, E. C., Smoller, J. W., & Sabuncu, M. R. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.01.029 · Cited by 29 · see citing works
Self-citationYan, Q., Tiwari, H. K., Yi, N., Gao, G., Zhang, K., Lin, W., Lou, X., Cui, X., & Liu, N. (2015) · Human Heredity · doi:10.1159/000375409 · Cited by 28 · see citing works
FREGAT: an R package for region-based association analysis
Belonogova, N. M., Svishcheva, G. R., & Axenovich, T. I. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw160 · Cited by 28 · see citing works
Lee, D., Lee, G. K., Yoon, K., & Lee, J. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065396 · Cited by 26 · see citing works
Region-Based Association Test for Familial Data under Functional Linear Models
Svishcheva, G. R., Belonogova, N. M., & Axenovich, T. I. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128999 · Cited by 25 · see citing works
A Kernel Regression Approach to Gene‐Gene Interaction Detection for Case‐Control Studies
Larson, N. B., & Schaid, D. J. (2013) · Genetic Epidemiology · doi:10.1002/gepi.21749 · Cited by 25 · see citing works
FFBSKAT: Fast Family-Based Sequence Kernel Association Test
Svishcheva, G. R., Belonogova, N. M., & Axenovich, T. I. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099407 · Cited by 23 · see citing works
Risk Classification With an Adaptive Naive Bayes Kernel Machine Model
Minnier, J., Yuan, M., Liu, J. S., & Cai, T. (2014) · Journal of the American Statistical Association · doi:10.1080/01621459.2014.908778 · Cited by 24 · see citing works
Global Analysis of Methylation Profiles From High Resolution CpG Data
Zhao, N., Bell, D. A., Maity, A., Staicu, A., Joubert, B. R., London, S. J., & Wu, M. C. (2014) · Genetic Epidemiology · doi:10.1002/gepi.21874 · Cited by 23 · see citing works
Alam, M. A., Lin, H.-Y., Deng, H., Calhoun, V. D., & Wang, Y. (2018) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2018.08.027 · Cited by 23 · see citing works
ExPheWas: a platform for cis -Mendelian randomization and gene-based association scans
Legault, M., Perreault, L. L., Tardif, J., & Dubé, M. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac289 · Cited by 22 · see citing works
Identification of genetic association of multiple rare variants using collapsing methods
Sun, Y. V., Sung, Y. J., Tintle, N., & Ziegler, A. (2011) · Genetic Epidemiology · doi:10.1002/gepi.20658 · Cited by 21 · see citing works
Imaging genetics — towards discovery neuroscience
Ge, T., Schumann, G., & Feng, J. (2013) · Quantitative Biology · doi:10.1007/s40484-013-0023-1 · Cited by 20 · see citing works
A variance component based multi-marker association test using family and unrelated data
Wang, X., Morris, N. J., Zhu, X., & Elston, R. C. (2013) · BMC Genetics · doi:10.1186/1471-2156-14-17 · Cited by 20 · see citing works
Identifying genetic marker sets associated with phenotypes via an efficient adaptive score test
Cai, T., Lin, X., & Carroll, R. J. (2012) · Biostatistics · doi:10.1093/biostatistics/kxs015 · Cited by 20 · see citing works
Self-citationYoo, Y. J., Sun, L., Poirier, J. G., Paterson, A. D., & Bull, S. B. (2016) · Genetic Epidemiology · doi:10.1002/gepi.22024 · Cited by 19 · see citing works
Zhao, L. P., & Bolouri, H. (2016) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2016.03.001 · Cited by 19 · see citing works
Chun, H., Ballard, D. H., Cho, J. H., & Zhao, H. (2011) · Genetic Epidemiology · doi:10.1002/gepi.20596 · Cited by 18 · see citing works
Modeling longitudinal imaging biomarkers with parametric Bayesian multi‐task learning
Aksman, L., Scelsi, M. A., Marquand, A. F., Alexander, D. C., Sebastien Ourselin, A., Altmann, A., & for, A. D. N. I. (2019) · Human Brain Mapping · doi:10.1002/hbm.24682 · Cited by 18 · see citing works
Associations of Progesterone Receptor Polymorphisms with Age at Menarche and Menstrual Cycle Length
Taylor, K. C., Small, C. M., Epstein, M. P., Sherman, S. L., Tang, W., Wilson, M. M., Bouzyk, M., & Marcus, M. (2010) · Hormone Research in Paediatrics · doi:10.1159/000316961 · Cited by 18 · see citing works
Self-citationIntegrative modeling of multi-platform genomic data under the framework of mediation analysis
Huang, Y. (2015) · Statistics in Medicine · doi:10.1002/sim.6326 · Cited by 17 · see citing works
Yan, Q., Weeks, D. E., Celedon, J. C., Tiwari, H. K., Li, B., Wang, X., Lin, W., Lou, X., Gao, G., Chen, W., et al. (2015) · Genetics · doi:10.1534/genetics.115.178590 · Cited by 17 · see citing works
Lu, H., Zhang, J., Jiang, Z., Zhang, M., Wang, T., Zhao, H., & Zeng, P. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.656545 · Cited by 17 · see citing works
Zeng, P., Zhao, Y., Li, H., Ting, W., & Chen, F. (2015) · BMC Medical Research Methodology · doi:10.1186/s12874-015-0030-1 · Cited by 17 · see citing works
A Generalized Genetic Random Field Method for the Genetic Association Analysis of Sequencing Data
Li, M., He, Z., Zhang, M., Zhan, X., Wei, C., Elston, R. C., & Lu, Q. L. (2014) · Genetic Epidemiology · doi:10.1002/gepi.21790 · Cited by 16 · see citing works
Broadaway, K. A., Duncan, R., Conneely, K. N., Almli, L. M., Bradley, B., Ressler, K. J., & Epstein, M. P. (2015) · Genetic Epidemiology · doi:10.1002/gepi.21901 · Cited by 15 · see citing works
Self-citationStructured Genome-Wide Association Studies with Bayesian Hierarchical Variable Selection
Zhao, Y., Hongtu Zhu, B., Lu, Z., Knickmeyer, R. C., & Zou, F. (2019) · Genetics · doi:10.1534/genetics.119.301906 · Cited by 16 · see citing works
Simpson, C. L., Wojciechowski, R., Yee, S. S., Soni, P., Wilson, J., & Stambolian, D. (2013) · Europe PMC (PubMed Central) · Cited by 16 · see citing works
Shao, Z., Wang, T., Zhang, M., Jiang, Z., Huang, S., & Zeng, P. (2021) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1009250 · Cited by 15 · see citing works
A Fast Multiple‐Kernel Method With Applications to Detect Gene‐Environment Interaction
West, R. M., Lu, W., Holloway, S. T., Sale, M. M., Worrall, B. B., Williams, S. R., Hsu, F., & Tzeng, J. (2015) · Genetic Epidemiology · doi:10.1002/gepi.21909 · Cited by 15 · see citing works
Rare-Variant Kernel Machine Test for Longitudinal Data from Population and Family Samples
Yan, Q., Weeks, D. E., Tiwari, H. K., Yi, N., Zhang, K., Gao, G., Lin, W., Lou, X., Chen, W., & Liu, N. (2015) · Human Heredity · doi:10.1159/000445057 · Cited by 15 · see citing works
On Optimal Gene‐Based Analysis of Genome Scans
Bacanu, S. (2012) · Genetic Epidemiology · doi:10.1002/gepi.21625 · Cited by 14 · see citing works
A unified framework for multi-locus association analysis of both common and rare variants
Shriner, D., & Vaughan, L. K. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-89 · Cited by 14 · see citing works
U-statistics in genetic association studies
Li, H. (2012) · Human Genetics · doi:10.1007/s00439-012-1178-y · Cited by 14 · see citing works
- Authors
- Kwee, L. C., Liu, D., Lin, X., Ghosh, D., & Epstein, M. P.
- Affiliations
- Emory University (US)
- Brown University (US)
- Harvard University (US)
- Pennsylvania State University (US)
- Corresponding author
- Epstein, Michael P.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 82
- Issue
- 2
- Pages
- 386-397
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC2664991
- OpenAlex
- W2164143816
- Cited by
- 227
- References
- 49
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 8 · 2019: 12 · 2018: 14 · 2017: 12 · 2016: 17 · 2015: 19 · 2014: 24 · 2013: 22 · 2012: 21
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Collection of Biostatistics Research Archive (submittedVersion)
- Funders
- National Institutes of Health (5t32gm074909-07)
- National Human Genome Research Institute (HG003618, R01HG003618)
- National Cancer Institute (R01CA076404, R37CA076404, CA76404, R29CA076404)
- National Institute of General Medical Sciences (T32-GM074909, GM074909)
- 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 and phenotypic traits in livestock
- Keywords
- quantitative trait mapping, tag SNPs, linkage disequilibrium, linear mixed models, semiparametric models, dimensionality reduction, statistical power, haplotypes, environmental variables
- MeSH terms
- Chromosome Mapping, Computer Simulation, Models, Genetic, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Quantitative Trait 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
