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Am J Hum Genet. 1989 Apr; 44(4): 543–551.
PMCID: PMC1715589

Estimating the power of a proposed linkage study for a complex genetic trait.


Many genetic traits have complex modes of inheritance; they may exhibit incomplete or age-dependent penetrance or fail to show any clear Mendelian inheritance pattern. As primary linkage maps for the human genome near completion, it is becoming increasingly possible to map these traits. Prior to undertaking a linkage study, it is important to consider whether the pedigrees available for the proposed study are likely to provide sufficient information to demonstrate linkage, assuming a linked marker is tested. In the current paper, we describe a computer simulation method to estimate the power of a proposed study to detect linkage for a complex genetic trait, given a hypothesized genetic model for the trait. Our method simulates trait locus genotypes consistent with observed trait phenotypes, in such a way that the probability to detect linkage can be estimated by sample statistics of the maximum lod score distribution. The method uses terms available when calculating the likelihood of the trait phenotypes for the pedigree and is applicable to any trait determined by one or a few genetic loci; individual-specific environmental effects can also be dealt with. Our method provides an objective answer to the question, Will these pedigrees provide sufficient information to map this complex genetic trait?

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Selected References

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  • Blackwelder WC, Elston RC. A comparison of sib-pair linkage tests for disease susceptibility loci. Genet Epidemiol. 1985;2(1):85–97. [PubMed]
  • Boehnke M. Estimating the power of a proposed linkage study: a practical computer simulation approach. Am J Hum Genet. 1986 Oct;39(4):513–527. [PMC free article] [PubMed]
  • Cavalli-Sforza LL, King MC. Detecting linkage for genetically heterogeneous diseases and detecting heterogeneity with linkage data. Am J Hum Genet. 1986 May;38(5):599–616. [PMC free article] [PubMed]
  • Donis-Keller H, Green P, Helms C, Cartinhour S, Weiffenbach B, Stephens K, Keith TP, Bowden DW, Smith DR, Lander ES, et al. A genetic linkage map of the human genome. Cell. 1987 Oct 23;51(2):319–337. [PubMed]
  • Elston RC, Bonney GE. Sampling considerations in the design and analysis of family studies. Prog Clin Biol Res. 1984;147:349–371. [PubMed]
  • Elston RC, Stewart J. A general model for the genetic analysis of pedigree data. Hum Hered. 1971;21(6):523–542. [PubMed]
  • Goldin LR, Gershon ES. Power of the affected-sib-pair method for heterogeneous disorders. Genet Epidemiol. 1988;5(1):35–42. [PubMed]
  • Hodge SE, Anderson CE, Neiswanger K, Sparkes RS, Rimoin DL. The search for heterogeneity in insulin-dependent diabetes mellitus (IDDM): linkage studies, two-locus models, and genetic heterogeneity. Am J Hum Genet. 1983 Nov;35(6):1139–1155. [PMC free article] [PubMed]
  • Kravitz K, Skolnick M, Cannings C, Carmelli D, Baty B, Amos B, Johnson A, Mendell N, Edwards C, Cartwright G. Genetic linkage between hereditary hemochromatosis and HLA. Am J Hum Genet. 1979 Sep;31(5):601–619. [PMC free article] [PubMed]
  • Lange K, Boehnke M. Extensions to pedigree analysis. V. Optimal calculation of Mendelian likelihoods. Hum Hered. 1983;33(5):291–301. [PubMed]
  • Lathrop GM, Lalouel JM, Julier C, Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. [PMC free article] [PubMed]
  • Ott J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet. 1974 Sep;26(5):588–597. [PMC free article] [PubMed]
  • Skolnick MH, Bishop DT, Cannings C, Hasstedt SJ. The impact of RFLPs on human gene mapping. Prog Clin Biol Res. 1984;147:271–292. [PubMed]
  • Thompson EA, Cannings C, Skolnick MH. Ancestral inference. I. The problem and the method. Ann Hum Genet. 1978 Jul;42(1):95–108. [PubMed]
  • Wong FL, Cantor RM, Rotter JI. Sample-size considerations and strategies for linkage analysis in autosomal recessive disorders. Am J Hum Genet. 1986 Jul;39(1):25–37. [PMC free article] [PubMed]

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