assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblingsassumption-free从全基因组遗传力估计identity-by-descent完整的兄弟姐妹之间共享.pdfVIP

Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings * Peter M. Visscher , Sarah E. Medland, Manuel A. R. Ferreira, Katherine I. Morley, Gu Zhu, Belinda K. Cornes, Grant W. Montgomery, Nicholas G. Martin Genetic Epidemiology Group, Queensland Institute of Medical Research, Brisbane, Australia 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