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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1990 Aug;47(2):247–254.

A multivariate method for detecting genetic linkage, with application to a pedigree with an adverse lipoprotein phenotype.

C I Amos 1, R C Elston 1, G E Bonney 1, B J Keats 1, G S Berenson 1
PMCID: PMC1683708  PMID: 2378349

Abstract

The robust or model-free method for detecting linkage developed by Haseman and Elston for data from sib pairs is extended to incorporate observations of multiple traits on each individual. A method is proposed that estimates the linear function that results in the strongest correlation between the squared pair differences in the trait measurements and identity by descent at a marker locus. The method is illustrated by the study of apolipoprotein and cholesterol levels in individuals from a large family that had many members diagnosed with coronary heart disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albers J. J., Utermann G. Genetic control of lecithin-cholesterol acyltransferase (LCAT): measurement of LCAT mass in a large kindred with LCAT deficiency. Am J Hum Genet. 1981 Sep;33(5):702–708. [PMC free article] [PubMed] [Google Scholar]
  2. Amos C. I., Elston R. C., Srinivasan S. R., Wilson A. F., Cresanta J. L., Ward L. J., Berenson G. S. Linkage and segregation analyses of apolipoproteins A1 and B, and lipoprotein cholesterol levels in a large pedigree with excess coronary heart disease: the Bogalusa Heart Study. Genet Epidemiol. 1987;4(2):115–128. doi: 10.1002/gepi.1370040206. [DOI] [PubMed] [Google Scholar]
  3. Amos C. I., Elston R. C., Wilson A. F., Bailey-Wilson J. E. A more powerful robust sib-pair test of linkage for quantitative traits. Genet Epidemiol. 1989;6(3):435–449. doi: 10.1002/gepi.1370060306. [DOI] [PubMed] [Google Scholar]
  4. Amos C. I., Wilson A. F., Rosenbaum P. A., Srinivasan S. R., Webber L. S., Elston R. C., Berenson G. S. An approach to the multivariate analysis of high-density-lipoprotein cholesterol in a large kindred: the Bogalusa Heart Study. Genet Epidemiol. 1986;3(4):255–267. doi: 10.1002/gepi.1370030406. [DOI] [PubMed] [Google Scholar]
  5. Bailey-Wilson J. E., Elston R. C., Wilson A. F., Amos C. I. A comparison of some sib-pair linkage methods and multiple locus extensions. Prog Clin Biol Res. 1989;329:129–134. [PubMed] [Google Scholar]
  6. Bonney G. E., Lathrop G. M., Lalouel J. M. Combined linkage and segregation analysis using regressive models. Am J Hum Genet. 1988 Jul;43(1):29–37. [PMC free article] [PubMed] [Google Scholar]
  7. Bonney G. E. On the statistical determination of major gene mechanisms in continuous human traits: regressive models. Am J Med Genet. 1984 Aug;18(4):731–749. doi: 10.1002/ajmg.1320180420. [DOI] [PubMed] [Google Scholar]
  8. Elston R. C., Namboodiri K. K., Glueck C. J., Fallat R., Tsang R., Leuba V. Study of the genetic transmission of hypercholesterolemia and hypertriglyceridemia in a 195 member kindred. Ann Hum Genet. 1975 Jul;39(1):67–87. doi: 10.1111/j.1469-1809.1975.tb00109.x. [DOI] [PubMed] [Google Scholar]
  9. Faust R. A., Cheung M. C., Albers J. J. Secretion of cholesteryl ester transfer protein-lipoprotein complexes by human HepG2 hepatocytes. Atherosclerosis. 1989 May;77(1):77–82. doi: 10.1016/0021-9150(89)90012-9. [DOI] [PubMed] [Google Scholar]
  10. Goldin L. R., Elston R. C., Graham J. B., Miller C. H. Genetic analysis of von Willebrand's disease in two large pedigrees: a multivariate approach. Am J Med Genet. 1980;6(4):279–293. doi: 10.1002/ajmg.1320060405. [DOI] [PubMed] [Google Scholar]
  11. Haseman J. K., Elston R. C. The investigation of linkage between a quantitative trait and a marker locus. Behav Genet. 1972 Mar;2(1):3–19. doi: 10.1007/BF01066731. [DOI] [PubMed] [Google Scholar]
  12. Hill A. P. Quantitative linkage: a statistical procedure for its detection and estimation. Ann Hum Genet. 1975 May;38(4):439–449. doi: 10.1111/j.1469-1809.1975.tb00633.x. [DOI] [PubMed] [Google Scholar]
  13. Jayakar S. D. 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] [Google Scholar]
  14. Kidd K. K., Kidd J. R., Castiglione C. M., Pakstis A. J., Sparkes R. S. Progress toward resolving the possible linkage of multiple endocrine neoplasia type 2A to haptoglobin and group-specific loci: use of restriction fragment length polymorphisms extends exclusion region. Genet Epidemiol. 1986;3(3):195–200. doi: 10.1002/gepi.1370030306. [DOI] [PubMed] [Google Scholar]
  15. LOWRY D. C., SHULTZ F. T. Testing association of metric traits and marker genes. Ann Hum Genet. 1959 Apr;23(2):83–90. doi: 10.1111/j.1469-1809.1958.tb01454.x. [DOI] [PubMed] [Google Scholar]
  16. Lange K., Boehnke M. Extensions to pedigree analysis. IV. Covariance components models for multivariate traits. Am J Med Genet. 1983 Mar;14(3):513–524. doi: 10.1002/ajmg.1320140315. [DOI] [PubMed] [Google Scholar]
  17. Lusis A. J., Zollman S., Sparkes R. S., Klisak I., Mohandas T., Drayna D., Lawn R. M. Assignment of the human gene for cholesteryl ester transfer protein to chromosome 16q12-16q21. Genomics. 1987 Nov;1(3):232–235. doi: 10.1016/0888-7543(87)90049-8. [DOI] [PubMed] [Google Scholar]
  18. Namboodiri K. K., Elston R. C., Glueck C. J., Fallat R., Buncher C. R., Tsang R. Bivariate analyses of cholesterol and triglyceride levels in families in which probands have type IIb lipoprotein phenotype. Am J Hum Genet. 1975 Jul;27(4):454–471. [PMC free article] [PubMed] [Google Scholar]
  19. Risch N. Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs. Am J Hum Genet. 1990 Feb;46(2):242–253. [PMC free article] [PubMed] [Google Scholar]
  20. Rosenbaum P. A., Amos C. I., Shear C. L., Elston R. C., Sellers T. A., Srinivasan S. R., Berenson G. S. Description of a large pedigree with an adverse lipoprotein cholesterol phenotype: the Bogalusa Heart Study. Genet Epidemiol. 1986;3(4):241–253. doi: 10.1002/gepi.1370030405. [DOI] [PubMed] [Google Scholar]
  21. Teisberg P., Gjone E., Olaisen B. Genetics of LCAT (lecithin: cholesterol acyltransferase) deficiency. Ann Hum Genet. 1975 Jan;38(3):327–331. doi: 10.1111/j.1469-1809.1975.tb00617.x. [DOI] [PubMed] [Google Scholar]
  22. Zlotnik L. H., Elston R. C., Namboodiri K. K. Pedigree discriminant analysis: a method to identify monogenic segregation. Am J Med Genet. 1983 Jun;15(2):307–313. doi: 10.1002/ajmg.1320150214. [DOI] [PubMed] [Google Scholar]

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