Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings

Visscher, Peter M., Medland, Sarah E., Ferreira, Manuel A. R., Morley, Katherine I., Zhu, Gu, Cornes, Belinda K., Montgomery, Grant W. and Martin, Nicholas G. (2006) Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings. Plos Genetics, 2 3: 316-325.


Author Visscher, Peter M.
Medland, Sarah E.
Ferreira, Manuel A. R.
Morley, Katherine I.
Zhu, Gu
Cornes, Belinda K.
Montgomery, Grant W.
Martin, Nicholas G.
Title Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings
Journal name Plos Genetics  (ERA 2012 Listed)    (ERA 2010 Rank A)   Check publisher's open access policy
Publication date 2006-03-24
Sub-type Article
DOI 10.1371/journal.pgen.0020041
Volume number 2
Issue number 3
ISSN 1553-7390; 1553-7404
Start page 316
End page 325
Total pages 10
Editor W. N. Frankel
Place of publication San Francisco, United States
Publisher Public Library of Science
Collection year 2006
Language eng
Subject 321011 Medical Genetics
730107 Inherited diseases (incl. gene therapy)
Abstract The study of continuously varying, quantitative traits is important in evolutionary biology, agriculture, and medicine. Variation in such traits is attributable to many, possibly interacting, genes whose expression may be sensitive to the environment, which makes their dissection into underlying causative factors difficult. An important population parameter for quantitative traits is heritability, the proportion of total variance that is due to genetic factors. Response to artificial and natural selection and the degree of resemblance between relatives are all a function of this parameter. Following the classic paper by R. A. Fisher in 1918, the estimation of additive and dominance genetic variance and heritability 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 identity-by-descent sharing, which varied from 0.374 to 0.617 (mean 0.498, standard deviation 0.036). The variance in identity-by-descent sharing per chromosome and per genome 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.
Keyword Genetics and heredity
Equal-environment assumption
Quantitative trait loci
Pair genetic identity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

 
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