The contribution of genetic variants to disease depends on the ruler

Witte, John S., Visscher, Peter M. and Wray, Naomi R. (2014) The contribution of genetic variants to disease depends on the ruler. Nature Reviews Genetics, 15 11: 765-776. doi:10.1038/nrg3786

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Author Witte, John S.
Visscher, Peter M.
Wray, Naomi R.
Title The contribution of genetic variants to disease depends on the ruler
Journal name Nature Reviews Genetics   Check publisher's open access policy
ISSN 1471-0056
Publication date 2014-11-25
Year available 2014
Sub-type Article (original research)
DOI 10.1038/nrg3786
Open Access Status File (Author Post-print)
Volume 15
Issue 11
Start page 765
End page 776
Total pages 12
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1312 Molecular Biology
1311 Genetics
2716 Genetics (clinical)
Abstract Our understanding of the genetic basis of disease has evolved from descriptions of overall heritability or familiality to the identification of large numbers of risk loci. One can quantify the impact of such loci on disease using a plethora of measures, which can guide future research decisions. However, different measures can attribute varying degrees of importance to a variant. In this Analysis, we consider and contrast the most commonly used measures-specifically, the heritability of disease liability, approximate heritability, sibling recurrence risk, overall genetic variance using a logarithmic relative risk scale, the area under the receiver-operating curve for risk prediction and the population attributable fraction-and give guidelines for their use that should be explicitly considered when assessing the contribution of genetic variants to disease.
Formatted abstract
Key points• Introduction• Measures of genetic impact for individual risk loci• Comparison of measures for single variants• Contribution of multiple risk loci to disease• Application to complex diseases• PAF: a problematic measure• Measures depend on the overall disease risk• Focus on the mean or the variance?• Extensions and additional measures• Conclusions and future perspectives• References• Acknowledgements• Author information• Supplementary information• Related links• Glossary
Keyword Genetics & Heredity
Genetics & Heredity
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID R01 CA088164
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 40 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 42 times in Scopus Article | Citations
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