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posted 13. February 2006 07:31
Source: PLoS Journals: PLoS Genetics
Assumption-free Estimation of Heritability^ from Genome-wide Identity-by-descent Sharing between Fullsibs
Peter M. Visscher, Sarah E. Medland, Manuel A.R. Ferreira, Katherine I. Morley, Gu Zhu, Belinda K. Cornes, Grant W. Montgomery, Nicholas G. Martin
PROVISIONAL ABSTRACT
Following the classic paper by R.A. Fisher in 1918, the estimation of additive and dominance genetic variance in populations is based upon the expected proportion of genes shared between different types of relatives and explicit, often controversial and untestable, models of genetic and non-genetic causes of family resemblance. With genome^-wide coverage of genetic markers it is now possible to estimate such parameters solely within families using the actual degree of identity-by-descent sharing between relatives. Using genome scans on 4,401 quasi-independent sib pairs of which 3,375 pairs had phenotypes^, we estimated the heritability of height from empirical genome-wide IBD sharing which varied from 0.374 to 0.617 (mean 0.498, SD 0.036). The variance in genome-wide sharing per chromosome^ and genome-wide was consistent with theory. The maximum likelihood estimate of the heritability for height was 0.80 with no evidence for non-genetic causes of sib resemblance, consistent with results from independent twin and family studies but using an entirely separate source of information. Our application shows that it is feasible to estimate genetic variance solely from within-family segregation and provides an independent validation of previously untestable assumptions. Given sufficient data, our new paradigm will allow the estimation of genetic variation for disease susceptibility and quantitative traits that is free from confounding with non-genetic factors and will allow partitioning of genetic variation into additive and non-additive components.
Received: December 7, 2005; Accepted: February 6, 2006
Provisional DOI: 10.1371/journal.pgen.0020041.eor
Copyright: © 2006 Visscher et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Editor: Trudy Mackay, North Carolina State University, Department of Genetics, Raleigh, NC, United States of America
¤ To whom correspondence should be addressed. E-mail: peter.visscher@qimr.edu.au
[Emphases added by ISCID News Editor]
[Link-underlined terms with ^ indicate linked entry in ISCID Encyclopedia of Science and Philosophy as added by ISCID News Editor]
View the original provisional abstract at PLoS Journals: PLoS Genetics
[ 13. February 2006, 07:33: Message edited by: ISCID News Editor ]
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