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

Visscher, PM; Medland, SE; Ferreira, MAR; Morley, KI; Zhu, G; Cornes, BK; Montgomery, GW; (2006) Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings. PLoS Genetics , 2 (3) , Article e41. 10.1371/journal.pgen.0020041. Green open access

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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.

Type: Article
Title: Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pgen.0020041
Publisher version: http://dx.doi.org/10.1371/journal.pgen.0020041
Language: English
Additional information: © 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. The adolescent genome scans were carried out at the Australian Genome Research Facility, Melbourne (Director, Dr. Sue Forrest) under a NHMRC Program in Medical Genomics grant to GWN and NGM, and at the Center for Inherited Disease Research, Baltimore (Director, Dr. Jerry Roberts) under a grant to Dr. Jeff Trent and NGM. This research was supported in part by grants from NIAAA (United States) AA007535, AA013320, AA013326, AA014041, AA07728, AA10249, and AA11998, and NHMRC (Australia) 941177, 951023, 950998, 981339, 241916, 241944, 339446, and 389892.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
URI: http://discovery.ucl.ac.uk/id/eprint/1359292
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