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Review
. 2009 Oct 8;461(7265):747-53.
doi: 10.1038/nature08494.

Finding the missing heritability of complex diseases

Teri A Manolio  1 , Francis S Collins, Nancy J Cox, David B Goldstein, Lucia A Hindorff, David J Hunter, Mark I McCarthy, Erin M Ramos, Lon R Cardon, Aravinda Chakravarti, Judy H Cho, Alan E Guttmacher, Augustine Kong, Leonid Kruglyak, Elaine Mardis, Charles N Rotimi, Montgomery Slatkin, David Valle, Alice S Whittemore, Michael Boehnke, Andrew G Clark, Evan E Eichler, Greg Gibson, Jonathan L Haines, Trudy F C Mackay, Steven A McCarroll, Peter M Visscher
Affiliations
Review

Finding the missing heritability of complex diseases

Teri A Manolio et al. Nature. .

Abstract

Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.

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Figures

Figure 1
Figure 1. Feasibility of identifying genetic variants by risk allele frequency and strength of genetic effect (odds ratio)
Most emphasis and interest lies in identifying associations with characteristics shown within diagonal dotted lines. Adapted from ref. 42.
See this image and copyright information in PMC

Comment in

References

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