Genome partitioning of genetic variation for height from 11,214 sibling pairs.
Height has been used for more than a century as a model by which to understand quantitative genetic variation in humans. We report that the entire genome appears to contribute to its additive genetic variance. We used genotypes and phenotypes of 11,214 sibling pairs from three countries to partition additive genetic variance across the genome. Using genome scans to estimate the proportion of the genomes of each chromosome from siblings that were identical by descent, we estimated the heritability of height contributed by each of the 22 autosomes and the X chromosome. We show that additive genetic variance is spread across multiple chromosomes and that at least six chromosomes (i.e., 3, 4, 8, 15, 17, and 18) are responsible for the observed variation. Indeed, the data are not inconsistent with a uniform spread of trait loci throughout the genome. Our estimate of the variance explained by a chromosome is correlated with the number of times suggestive or significant linkage with height has been reported for that chromosome. Variance due to dominance was not significant but was difficult to assess because of the high sampling correlation between additive and dominance components. Results were consistent with the absence of any large between-chromosome epistatic effects. Notwithstanding the proposed architecture of complex traits that involves widespread gene-gene and gene-environment interactions, our results suggest that variation in height in humans can be explained by many loci distributed over all autosomes, with an additive mode of gene action.
Visscher
Peter M
PM
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia. peter.visscher@qimr.edu.au
Macgregor
Stuart
S
Benyamin
Beben
B
Zhu
Gu
G
Gordon
Scott
S
Medland
Sarah
S
Hill
William G
WG
Hottenga
Jouke-Jan
JJ
Willemsen
Gonneke
G
Boomsma
Dorret I
DI
Liu
Yao-Zhong
YZ
Deng
Hong-Wen
HW
Montgomery
Grant W
GW
Martin
Nicholas G
NG
D001315:Australia; D001827:Body Height / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D030541:Databases, Genetic; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D019655:Quantitative Trait, Heritable; D035781:Siblings; D014481:United States