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Multifactorial genetics

Wake-up call for genome scanners

Nature Reviews Genetics volume 3, page 9 (2002)Cite this article

The primary goal of a genome scan is to find the genetic loci that influence a particular phenotypic trait. If evidence for a locus is found, it is also very useful to know the locus effect size—how much of the heritability of the phenotype is attributable to variation at that locus. And that's where the problem lies. The position of the locus is estimated by the LOD score, which measures the likelihood of linkage at any given location, but because the LOD score is positively correlated with the effect size of the locus, the location and the heritability of the locus cannot be estimated independently from the same data set.

To study this phenomenon—which has been well documented in experimental species—in the context of human genetics, Göring et al. simulated and mathematically analysed a fairly typical genome scanning experiment: the hypothetical population comprises 1,000 families, each with two offspring; the trait being modelled has a heritability of 0.5, with variable numbers of QTL; genotypic data are available from markers at 2-cM intervals; and there are no complicating factors such as epistatic or gene–environment interactions. But even with this well-behaved data set, the authors found that there is no way to reliably estimate the heritability effect of any QTL. Their mathematical analysis of the problem shows that the QTL effect is always overestimated, although this bias does fall away with increasing sample size.

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References

ORIGINAL RESEARCH PAPER

  1. Göring, H. H. H. et al. Large upward bias in estimation of locus-specific effects from genomewide scans. Am. J. Hum. Genet. 69, 1357–1369 (2001)

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FURTHER READING

  1. Cardon, L. & Bell, J. Association study designs for complex diseases. Nature Rev. Genet. 2, 91–99 (2001)

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Authors
  1. Mark Patterson
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Patterson, M. Wake-up call for genome scanners. Nat Rev Genet 3, 9 (2002). https://doi.org/10.1038/nrg709

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