Wake-up call for genome scanners

Access through your institution Buy or subscribe 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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calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL RESEARCH PAPER *

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) Article  Google Scholar  FURTHER READING *

Cardon, L. & Bell, J. Association study designs for complex diseases. _Nature Rev. Genet_. 2, 91–99 (2001) Article  CAS  Google Scholar  Download references Authors * Mark Patterson View

author publications You can also search for this author inPubMed Google Scholar RELATED LINKS RELATED LINKS WEB SITES John Blangero's lab RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Patterson, M. Wake-up call for genome scanners. _Nat Rev Genet_ 3, 9 (2002). https://doi.org/10.1038/nrg709 Download citation * Issue Date:

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