Combined Linkage and Association Sib-Pair Analysis for Quantitative Traits
Open accessAbstract
An extension to current maximum-likelihood variance-components procedures for mapping quantitative-trait loci in sib pairs that allows a simultaneous test of allelic association is proposed. The method involves modeling of the allelic means for a test of association, with simultaneous modeling of the sib-pair covariance structure for a test of linkage. By partitioning of the mean effect of a locus into between- and within-sibship components, the method controls for spurious associations due to population stratification and admixture. The power and efficacy of the method are illustrated through simulation of various models of both real and spurious association.
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?
Within-family genetic association estimates, such as those obtained from samples of siblings, can provide less biased estimates of direct genetic effects because they are unlikely to be affected by demographic and indirect genetic effects of parents.
“Within-family genetic association estimates, such as those obtained from samples of siblings, can provide less biased estimates of direct genetic effects because they are unlikely to be affected by demographic and indirect genetic effects of parents7,17,30–34.”
From Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects (2022) · cites this paper as [30]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Part of this paper’s reference list could not be split into single entries.
Research works printed but not linked: 18
- [1]1. Allison, DB Transmission-disequilibrium tests for quantitative traits Am J Hum Genet. 1997; 60:676-690 PubMed Google Scholar
- [2]2. Almasy, L ∙ Blangero, J Multipoint quantitative-trait linkage analysis in general pedigrees Am J Hum Genet. 1998; 62:1198-1211 Full Text Full Text (PDF) Scopus (2603) PubMed Google Scholar
- [3]3. Amos, CI Robust variance-components approach for assessing genetic linkage in pedigrees Am J Hum Genet. 1994; 54:535-543 PubMed Google Scholar
- [4]4. Boehnke, M ∙ Langefeld, CD Genetic association mapping based on discordant sib pairs: the discordant-alleles test Am J Hum Genet. 1998; 62:950-961 Full Text Full Text (PDF) Scopus (173) PubMed Google Scholar
- [5]5. Chorney, MJ ∙ Chorney, K ∙ Seese, N ... A quantitative trait locus associated with cognitive ability in children Psychol Sci. 1998; 9:159-166 Crossref Scopus (113) Google Scholar
- [6]6. Curtis, D Use of siblings as controls in case-control association studies Ann Hum Genet. 1997; 61:319-333 Crossref Scopus (176) PubMed Google Scholar
- [7]7. Curtis, D ∙ Sham, PC A note on the application of the transmission disequilibrium test when a parent is missing Am J Hum Genet. 1995; 56:811-812 PubMed Google Scholar
- [9]9. Fulker, DW ∙ Cherny, SS An improved multipoint sib-pair analysis of quantitative traits Behav Genet. 1996; 26:527-532 Crossref Scopus (125) PubMed Google Scholar
- [10]10. Haseman, JK ∙ Elston, RC The investigation of linkage between a quantitative trait and a marker locus Behav Genet. 1972; 2:3-19 Crossref Scopus (1061) PubMed Google Scholar
- [11]11. Kruglyak, L ∙ Lander, ES Complete multipoint sib-pair analysis of qualitative and quantitative traits Am J Hum Genet. 1995; 57:439-454 PubMed Google Scholar
- [12]12. Lazzeroni, LC ∙ Lange, K A conditional inference framework for extending the transmission/disequilibrium test Hum Hered. 1998; 48:67-81 Crossref Scopus (108) PubMed Google Scholar
- [13]13. Rabinowitz, D A transmission disequilibrium test for quantitative trait loci Hum Hered. 1997; 47:342-350 Crossref Scopus (200) PubMed Google Scholar
- [14]14. Sham, P Transmission/disequilibrium tests for multiallelic loci Am J Hum Genet. 1997; 61:774-778 Full Text (PDF) Scopus (28) PubMed Google Scholar
- [15]15. Sham, PC ∙ Curtis, D Monte Carlo tests for associations between disease and alleles at highly polymorphic loci Ann Hum Genet. 1995a; 59:97-105 Crossref Scopus (871) PubMed Google Scholar
- [16]16. Sham, PC ∙ Curtis, D An extended transmission/disequilibrium test (TDT) for multiallelic marker loci Ann Hum Genet. 1995b; 59:323-336 Crossref Scopus (586) PubMed Google Scholar
- [17]17. Spielman, RS ∙ Ewens, WJ A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test Am J Hum Genet. 1998; 62:450-458 Full Text Full Text (PDF) Scopus (562) PubMed Google Scholar
- [18]18. Spielman, RS ∙ McGinnis, RE ∙ Ewens, WJ Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM) Am J Hum Genet. 1993; 52:506-516 PubMed Google Scholar
- [19]19. Terwilliger, J ∙ Ott, J A haplotype-based “haplotype relative risk” approach to detecting allelic associations Hum Hered. 1992; 42:337-346 Crossref Scopus (444) PubMed Google Scholar
Cited by
Sorted by citations
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
Self-citationPurcell, S., Cherny, S. S., & Sham, P. C. (2003) · Bioinformatics · doi:10.1093/bioinformatics/19.1.149 · Cited by 2,057 · see citing works
Self-citationGenome-wide association studies
Uffelmann, E., Huang, Q. Q., Munung, N. S., de Vries, J., Okada, Y., Martin, A. R., Martin, H. C., Lappalainen, T., & Posthuma, D. (2021) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00056-9 · Cited by 1,849 · see citing works
Scuteri, A., Sanna, S., Chen, W.-M., Uda, M., Albai, G., Strait, J., Najjar, S., Nagaraja, R., Orrú, M., Usala, G., et al. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030115 · Cited by 1,724 · 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
Li, Y., Willer, C., Sanna, S., & Abecasis, G. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.9.081307.164242 · Cited by 990 · see citing works
Uda, M., Galanello, R., Sanna, S., Lettre, G., Sankaran, V. G., Chen, W., Usala, G., Busonero, F., Maschio, A., Albai, G., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711566105 · Cited by 672 · 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
Self-citationBrumpton, B., Sanderson, E., Heilbron, K., Hartwig, F. P., Harrison, S., Vie, G. Å., Cho, Y., Howe, L. D., Hughes, A., Boomsma, D. I., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17117-4 · Cited by 402 · see citing works
Theory and practice in quantitative genetics
Posthuma, D., Beem, A. L., de Geus, E. J. C., van Baal, G. C. M., von Hjelmborg, J. B., Iachine, I., & Boomsma, D. I. (2003) · Twin Research · doi:10.1375/136905203770326367 · Cited by 416 · see citing works
Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects
Howe, L. J., Nivard, M. G., Morris, T. T., Hansen, A. F., Rasheed, H., Cho, Y., Chittoor, G., Ahlskog, R., Lind, P. A., Palviainen, T., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01062-7 · Cited by 377 · see citing works
Self-citationD’Onofrio, B. M., Lahey, B. B., Turkheimer, E., & Lichtenstein, P. (2013) · American Journal of Public Health · doi:10.2105/ajph.2013.301252 · Cited by 343 · see citing works
A Note on the Statistical Power in Extended Twin Designs
Posthuma, D., & Boomsma, D. I. (2000) · Behavior Genetics · doi:10.1023/a:1001959306025 · Cited by 272 · see citing works
Iyengar, S. K., Song, D., Klein, B. E. K., Klein, R., Schick, J. H., Humphrey, J., Millard, C., Liptak, R., Russo, K., Jun, G., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/380912 · Cited by 173 · see citing works
Within family Mendelian randomization studies
Davies, N. M., Howe, L. J., Brumpton, B., Havdahl, A., Evans, D. M., & Davey Smith, G. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz204 · Cited by 158 · see citing works
Haberstick, B. C., Smolen, A., & Hewitt, J. K. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.008 · Cited by 112 · see citing works
Self-citationBehavior Genetic Research Methods: Testing Quasi-Causal Hypotheses Using Multivariate Twin Data
Turkheimer, E., & Harden, K. P. (2014) · Handbook of Research Methods in Social and Personality Psychology · doi:10.1017/cbo9780511996481.012 · Cited by 111 · see citing works
Genome-Wide Association Study of the Child Behavior Checklist Dysregulation Profile
Mick, E., McGough, J., Loo, S., Doyle, A. E., Wozniak, J., Wilens, T. E., Smalley, S., McCracken, J., Biederman, J., & Faraone, S. V. (2011) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2011.05.001 · Cited by 75 · see citing works
Mascheretti, S., Trezzi, V., Giorda, R., Boivin, M., Plourde, V., Vitaro, F., Brendgen, M., Dionne, G., & Marino, C. (2017) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12612 · Cited by 37 · see citing works
Ferreira, M. A. R., Sham, P., Daly, M. J., & Purcell, S. (2007) · Behavior Genetics · doi:10.1007/s10519-007-9149-0 · Cited by 15 · see citing works
Self-citationCombined linkage disequilibrium and linkage mapping: Bayesian multilocus approach
Pikkuhookana, P., & Sillanpää, M. J. (2014) · Heredity · doi:10.1038/hdy.2013.111 · Cited by 13 · see citing works
Wessel, J., Schork, A. J., Tiwari, H. K., & Schork, N. J. (2007) · Genetic Epidemiology · doi:10.1002/gepi.20241 · Cited by 12 · see citing works
- Authors
- Fulker, D. W., Cherny, S. S., Sham, P. C., & Hewitt, J. K.
- Affiliations
- University of London (GB)
- University of Colorado Boulder (US)
- Corresponding author
- Cherny, S.S.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 64
- Issue
- 1
- Pages
- 259-267
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1377724
- OpenAlex
- W2078343620
- Cited by
- 443
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 3 · 2016: 8 · 2015: 4 · 2014: 11 · 2013: 18 · 2012: 14
- FWCI
- 15.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- National Institutes of Health (5r01aa007330-12)
- National Institute on Alcohol Abuse and Alcoholism (AA10556, AA-07330)
- National Institute on Drug Abuse (DA11015, P60DA011015)
- 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 › Forensic and Genetic Research
- Keywords
- quantitative trait loci, sib-pair analysis, linkage analysis, allelic association, spurious association, population stratification, admixture
- MeSH terms
- Genotype, Humans, Genetic Linkage, Models, Genetic, Nuclear Family, Quantitative Trait, Heritable
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
