Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings

By Peter M. Visscher, S. Medland, M. Ferreira, K. Morley, G. Zhu, Belinda K. Cornes, G. Montgomery, Nicholas G. Martin. PLoS Genetics, 2006

641 citations recorded by the source corpus.

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.

Subfields: Genetics

View Paper: https://www.semanticscholar.org/paper/697a33357313a2b702dc4d6cfa67ac2f8e8cd34c

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Citations in the corpus

Defining the role of common variation in the genomic and biological architecture of adult human height (2014, background): “supporting evidence for a gene included (1) annotation by GRAIL, (2) differential expression within the growth plate, (3) specific expression within the growth plate, (4) a mouse”
Are Political Orientations Genetically Transmitted? (2005, methodology): “Visscher et al. (2006) used nontwin sibling’s exact genetic similarities (DNA) in a var-”
The Genetics of Human Adaptation: Hard Sweeps, Soft Sweeps, and Polygenic Adaptation (2010, neutral): “Since height is extremely heritable [69], many more loci remain to be found.”
The mystery of missing heritability: Genetic interactions create phantom heritability (2012, background): “The first (26) measures genotypic similarity in terms of IBD within sib pairs—essentially measuring ρ′(1/2), in our terminology.”
Increased accuracy of artificial selection by using the realized relationship matrix. (2009, background): “6, close to the reported empirical value of 82 for human full sibs (Visscher et al., 2006).”
Genomic selection: prediction of accuracy and maximisation of long term response (2009, methodology): “This is the same definition as used by Visscher et al. (2006). Consider a model of the genetic value (g) of gametes (i.”
The Impact of Genetic Architecture on Genome-Wide Evaluation Methods (2010, background): “His derivation builds on work by Visscher et al. (2006) in which the variance of identical-by-descent sharing for full sibs was developed and provides a prediction for Me, which is Me ¼ 2NeL/ log(4NeL), where L is the genome length in Morgans (Goddard 2009).”
New Answers for Old Questions: The Evolutionary Quantitative Genetics of Wild Animal Populations (2008, methodology): “A related approach has also recently been described by (Visscher et al. 2006).”
An expanded view of complex traits: from polygenic to omnigenic (2017, background): “However, it is known that the heritability contributed by each chromosome tends to be closely proportional to its physical length (Visscher et al., 2006; Shi et al., 2016), hinting that causal variants may be fairly uniformly distributed.”
coancestry: a program for simulating, estimating and analysing relatedness and inbreeding coefficients (2011, background): “Example applications include estimating heritabilities (e.g. Ritland 2000; Visscher et al. 2006), minimizing inbreeding in captive populations (e.”
Why are Normal Distributions Normal? (2014, background): “Third, it’s estimated that about 80% of human height is due to genetics (Visscher et al. [2006]).”