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 (x2 = 83.89, df = 1; p = 5.2610220). 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.