pmc logo image
Logo of ajhgJournal URL: http://www.cell.com/AJHG/

Formats:

Am J Hum Genet. 1994 March; 54(3): 535–543.
PMCID: PMC1918121
Robust variance-components approach for assessing genetic linkage in pedigrees.
C. I. Amos
Department of Epidemiology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Abstract
To assess evidence for genetic linkage from pedigrees, I developed a limited variance-components approach. In this method, variability among trait observations from individuals within pedigrees is expressed in terms of fixed effects from covariates and effects due to an unobservable trait-affecting major locus, random polygenic effects, and residual nongenetic variance. The effect attributable to a locus linked to a marker is a function of the additive and dominance components of variance of the locus, the recombination fraction, and the proportion of genes identical by descent at the marker locus for each pair of sibs. For unlinked loci, the polygenic variance component depends only on the relationship between the relative pair. Parameters can be estimated by either maximum-likelihood methods or quasi-likelihood methods. The forms of quasi-likelihood estimators are provided. Hypothesis tests derived from the maximum-likelihood approach are constructed by appeal to asymptotic theory. A simulation study showed that the size of likelihood-ratio tests was appropriate but that the monogenic component of variance was generally underestimated by the likelihood approach.
Full text
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
  • Amos CI, Dawson DV, Elston RC. The probabilistic determination of identity-by-descent sharing for pairs of relatives from pedigrees. Am J Hum Genet. 1990 Nov;47(5):842–853. [PubMed]
  • Amos CI, Elston RC. Robust methods for the detection of genetic linkage for quantitative data from pedigrees. Genet Epidemiol. 1989;6(2):349–360. [PubMed]
  • Amos CI, Elston RC, Wilson AF, Bailey-Wilson JE. A more powerful robust sib-pair test of linkage for quantitative traits. Genet Epidemiol. 1989;6(3):435–449. [PubMed]
  • BRUES AM. Linkage of body build with sex, eye color, and freckling. Am J Hum Genet. 1950 Sep;2(3):215–239. [PubMed]
  • Carey G, Williamson J. Linkage analysis of quantitative traits: increased power by using selected samples. Am J Hum Genet. 1991 Oct;49(4):786–796. [PubMed]
  • Demenais FM, Amos CI. Power of the sib-pair and lod-score methods for linkage analysis of quantitative traits. Prog Clin Biol Res. 1989;329:201–206. [PubMed]
  • Goldgar DE. Multipoint analysis of human quantitative genetic variation. Am J Hum Genet. 1990 Dec;47(6):957–967. [PubMed]
  • Haseman JK, Elston RC. The investigation of linkage between a quantitative trait and a marker locus. Behav Genet. 1972 Mar;2(1):3–19. [PubMed]
  • Jayakar SD. On the detection and estimation of linkage between a locus influencing a quantitative character and a marker locus. Biometrics. 1970 Sep;26(3):451–464. [PubMed]
  • Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM, et al. Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992 Oct 2;71(1):169–180. [PubMed]
  • Kammerer CM, MacCluer JW. Comparison of two preliminary methods of quantitative linkage analysis. Hum Hered. 1985;35(5):319–325. [PubMed]
  • Lander ES, Botstein D. Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics. 1989 Jan;121(1):185–199. [PubMed]
  • Lange K, Westlake J, Spence MA. Extensions to pedigree analysis. III. Variance components by the scoring method. Ann Hum Genet. 1976 May;39(4):485–491. [PubMed]
  • Olson JM, Wijsman EM. Linkage between quantitative trait and marker loci: methods using all relative pairs. Genet Epidemiol. 1993;10(2):87–102. [PubMed]
  • Prentice RL, Zhao LP. Estimating equations for parameters in means and covariances of multivariate discrete and continuous responses. Biometrics. 1991 Sep;47(3):825–839. [PubMed]
  • Schork NJ. Extended multipoint identity-by-descent analysis of human quantitative traits: efficiency, power, and modeling considerations. Am J Hum Genet. 1993 Dec;53(6):1306–1319. [PubMed]