Gene‐Trait Similarity Regression for Multimarker‐Based Association Analysis
Open accessAbstract
Summary We propose a similarity‐based regression method to detect associations between traits and multimarker genotypes. The model regresses similarity in traits for pairs of “unrelated” individuals on their haplotype similarities, and detects the significance by a score test for which the limiting distribution is derived. The proposed method allows for covariates, uses phase‐independent similarity measures to bypass the needs to impute phase information, and is applicable to traits of general types (e.g., quantitative and qualitative traits). We also show that the gene‐trait similarity regression is closely connected with random effects haplotype analysis, although commonly they are considered as separate modeling tools. This connection unites the classic haplotype sharing methods with the variance‐component approaches, which enables direct derivation of analytical properties of the sharing statistics even when the similarity regression model becomes analytically challenging.
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?
Approaches that capture subtle synergistic effects among many loci in a region, or among different variant types affecting gene function, such as sequence- or functional-similarity-based methods, are probably also suitable.
“However, methods which can account for subtle synergistic effects of many loci within a defined region and/or different forms of variation that might contribute to gene function, such as those rooted in sequence or functional similarity56, 57, 87, 88 are also likely to be appropriate.”
From Statistical analysis strategies for association studies involving rare variants (2010) · cites this paper as [57]
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
The International HapMap Project
†The International HapMap Consortium, Genotyping centres: Baylor College of Medicine and ParAllele BioScience, Gibbs, R. A., Belmont, J. W., Hardenbol, P., Willis, T. D., Yu, F., Chinese HapMap Consortium, Yang, H., Ch'ang, L.-Y., et al. (2003) · Nature · doi:10.1038/nature02168 · Cited by 6,057 · see citing works
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R., Ellis, M. C., Fullan, A., et al. (1996) · Nature Genetics · doi:10.1038/ng0896-399 · Cited by 3,664 · 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
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
The investigation of linkage between a quantitative trait and a marker locus
Haseman, J. K., & Elston, R. C. (1972) · Behavior Genetics · doi:10.1007/bf01066731 · Cited by 1,367 · see citing works
Computing the distribution of quadratic forms in normal variables
Imhof, J. P. (1961) · Biometrika · doi:10.1093/biomet/48.3-4.419 · Cited by 1,153 · see citing works
Houwen, R. H. J., Baharloo, S., Blankenship, K., Raeymaekers, P., Juyn, J., Sandkuijl, L. A., & Freimer, N. B. (1994) · Nature Genetics · doi:10.1038/ng1294-380 · Cited by 316 · see citing works
Evaluating associations of haplotypes with traits
Schaid, D. J. (2004) · Genetic Epidemiology · doi:10.1002/gepi.20037 · Cited by 315 · 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
On multiple‐testing correction in genome‐wide association studies
Moskvina, V., & Schmidt, K. M. (2008) · Genetic Epidemiology · doi:10.1002/gepi.20331 · Cited by 266 · see citing works
Puffenberger, E. G., Kauffman, E., Gabriel, S., Matise, T. C., Washington, S. S., Angrist, M. H., Weissenbach, J., Garver, K. L., Mascari, M. J., Ladda, R. L., et al. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.8.1217 · Cited by 244 · see citing works
Schymick, J. C., Scholz, S. W., Fung, H., Britton, A. F., Arepalli, S., Gibbs, J. R., Lombardo, F., Matarín, M., Kasperavičiūtė, D., Hernandez, D. G., et al. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70037-6 · Cited by 218 · 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
Assessing the performance of the haplotype block model of linkage disequilibrium.
Wall, J., & Pritchard, J. (2003) · American Journal of Human Genetics · doi:10.1086/378099 · Cited by 168 · see citing works
Equivalence between Haseman-Elston and Variance-Components Linkage Analyses for Sib Pairs
Sham, P. C., & Purcell, S. (2001) · The American Journal of Human Genetics · doi:10.1086/320593 · Cited by 135 · see citing works
Tzeng, J., Devlin, B., Wasserman, L., & Roeder, K. (2003) · The American Journal of Human Genetics · doi:10.1086/373881 · Cited by 135 · see citing works
Self-citationService, S. K., Lang, D. W. T., Freimer, N. B., & Sandkuijl, L. A. (1999) · The American Journal of Human Genetics · doi:10.1086/302398 · Cited by 112 · see citing works
Search for multifactorial disease susceptibility genes in founder populations
Bourgain, C., Génin, E., Quesneville, H., & Clerget‐Darpoux, F. (2000) · Annals of Human Genetics · doi:10.1046/j.1469-1809.2000.6430255.x · Cited by 77 · 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
Self-citationHaplotype Sharing Analysis Using Mantel Statistics
Beckmann, L., Thomas, D. C., Fischer, C., & Chang-Claude, J. C. (2005) · Human Heredity · doi:10.1159/000085221 · Cited by 59 · see citing works
Self-citationBourgain, C., Génin, E., Holopainen, P., Mustalahti, K., Mäki, M., Partanen, J., & Clerget‐Darpoux, F. (2001) · The American Journal of Human Genetics · doi:10.1086/316933 · Cited by 46 · see citing works
Molitor, J., Marjoram, P., & Thomas, D. C. (2003) · Genetic Epidemiology · doi:10.1002/gepi.10251 · Cited by 42 · see citing works
Self-citationOutlier Detection and False Discovery Rates for Whole-Genome DNA Matching
Tzeng, J., Byerley, W., Devlin, B., Roeder, K., & Wasserman, L. (2003) · Journal of the American Statistical Association · doi:10.1198/016214503388619256 · Cited by 33 · see citing works
Self-citationGenetic 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
Yu, K. F., Gu, C. C., Province, M. A., Xiong, C., & Rao, D. C. (2004) · Genetic Epidemiology · doi:10.1002/gepi.20022 · Cited by 33 · see citing works
Durham, L. K., & Feingold, E. (1997) · The American Journal of Human Genetics · doi:10.1086/514891 · Cited by 32 · see citing works
Resnick, H. E., Rodríguez, B. L., Havlik, R. J., Ferrucci, L., Foley, D. J., Curb, J. D., & Harris, T. B. (2000) · Genetic Epidemiology · doi:10.1002/1098-2272(200007)19:1 · Cited by 25 · see citing works
Genome Scan of Complex Traits by Haplotype Sharing Correlation
Qian, D., & Thomas, D. C. (2001) · Genetic Epidemiology · doi:10.1002/gepi.2001.21.s1.s582 · Cited by 24 · see citing works
Self-citationA new association test using haplotype similarity
Sha, Q., Chen, H., & Zhang, S. (2007) · Genetic Epidemiology · doi:10.1002/gepi.20230 · Cited by 24 · see citing works
Missing data in haplotype analysis: a study on the MILC method
Bourgain, C., Génin, E., Ober, C., et al. (2002) · Annals of Human Genetics · doi:10.1017/s000348000100896x · Cited by 23 · see citing works
Statistical Models for Haplotype Sharing in Case-Parent Trio Data
Allen, A. S., & Satten, G. A. (2007) · Human Heredity · doi:10.1159/000101421 · Cited by 22 · see citing works
Bayes Estimates of Haplotype Effects
Thomas, D. C., Morrison, J. L., & Clayton, D. G. (2001) · Genetic Epidemiology · doi:10.1002/gepi.2001.21.s1.s712 · Cited by 22 · see citing works
Self-citationMeasuring and partitioning the high‐order linkage disequilibrium by multiple order Markov chains
Kim, Y., Feng, S., & Zeng, Z. (2008) · Genetic Epidemiology · doi:10.1002/gepi.20305 · Cited by 16 · see citing works
Thomas, D. C., Qian, D., Gauderman, W. J., et al. (1999) · Genetic Epidemiology · doi:10.1002/gepi.13701707121 · Cited by 14 · see citing works
Self-citationMissing data in haplotype analysis: a study on the MILC method
Bourgain, C., Génin, E., Ober, C., et al. (2002) · Annals of Human Genetics · doi:10.1046/j.1469-1809.2002.6610099.x · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Statistical 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
Pan, W. (2011) · Genetic Epidemiology · doi:10.1002/gepi.20567 · Cited by 71 · see citing works
- Authors
- Tzeng, J., Zhang, D., Chang, S., Thomas, D. C., & Davidian, M.
- Affiliations
- North Carolina State University (US)
- National Cheng Kung University (TW)
- University of Southern California (US)
- Corresponding author
- Tzeng, Jung‐Ying
- Venue
- Biometrics
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-09
- Volume
- 65
- Issue
- 3
- Pages
- 822-832
- ISSN
- 0006-341X (ISSN-L)
- 1541-0420
- PMC
- PMC2748404
- OpenAlex
- W2145127560
- Cited by
- 50
- References
- 35
- Citations by year
- 2026: 2 · 2025: 1 · 2020: 1 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 6 · 2014: 7 · 2013: 7 · 2012: 6
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biometrics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation
- National Science Council
- National Institutes of Health
- National Institute of Mental Health (R01MH084022, R01MH074027)
- National Cancer Institute (R01CA052862, R01CA085848, R01 CA52862)
- National Institute of Neurological Disorders and Stroke
- National Institute of Environmental Health Sciences (U01ES015090, R01ES019876)
- 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
- haplotype sharing, score test, asymptotic distribution, quantitative traits, qualitative traits, variance component models
- MeSH terms
- Chromosome Mapping, Computer Simulation, Genetic Markers, Haplotypes, Humans, Genetic Linkage, Models, Genetic, Regression Analysis, Models, Statistical, 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
