Evidence of inbreeding depression on human height.

PLoS Genet 2012 19;8(7):e1002655. Epub 2012 Jul 19.

Centre for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom.

Stature is a classical and highly heritable complex trait, with 80%-90% of variation explained by genetic factors. In recent years, genome-wide association studies (GWAS) have successfully identified many common additive variants influencing human height; however, little attention has been given to the potential role of recessive genetic effects. Here, we investigated genome-wide recessive effects by an analysis of inbreeding depression on adult height in over 35,000 people from 21 different population samples. We found a highly significant inverse association between height and genome-wide homozygosity, equivalent to a height reduction of up to 3 cm in the offspring of first cousins compared with the offspring of unrelated individuals, an effect which remained after controlling for the effects of socio-economic status, an important confounder (χ(2) = 83.89, df = 1; p = 5.2 × 10(-20)). There was, however, a high degree of heterogeneity among populations: whereas the direction of the effect was consistent across most population samples, the effect size differed significantly among populations. It is likely that this reflects true biological heterogeneity: whether or not an effect can be observed will depend on both the variance in homozygosity in the population and the chance inheritance of individual recessive genotypes. These results predict that multiple, rare, recessive variants influence human height. Although this exploratory work focuses on height alone, the methodology developed is generally applicable to heritable quantitative traits (QT), paving the way for an investigation into inbreeding effects, and therefore genetic architecture, on a range of QT of biomedical importance.

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1002655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400549PMC
January 2013
150 Reads
31 Citations

Publication Analysis

Top Keywords

human height
12
population samples
8
inbreeding depression
8
height
7
high degree
4
degree heterogeneity
4
heterogeneity populations
4
10-20 high
4
8389 10-20
4
χ2 8389
4
populations direction
4
status confounder
4
confounder χ2
4
samples size
4
populations reflects
4
reflects true
4
true biological
4
differed populations
4
size differed
4
consistent population
4

Similar Publications