A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Evidence of Inbreeding Depression on Human Height
Tekijät: McQuillan R, Eklund N, Pirastu N, Kuningas M, McEvoy BP, Esko T, Corre T, Davies G, Kaakinen M, Lyytikainen LP, Kristiansson K, Havulinna AS, Gogele M, Vitart V, Tenesa A, Aulchenko Y, Hayward C, Johansson A, Boban M, Ulivi S, Robino A, Boraska V, Igl W, Wild SH, Zgaga L, Amin N, Theodoratou E, Polasek O, Girotto G, Lopez LM, Sala C, Lahti J, Laatikainen T, Prokopenko I, Kals M, Viikari J, Yang J, Pouta A, Estrada K, Hofman A, Freimer N, Martin NG, Kahonen M, Milani L, Heliovaara M, Vartiainen E, Raikkonen K, Masciullo C, Starr JM, Hicks AA, Esposito L, Kolcic I, Farrington SM, Oostra B, Zemunik T, Campbell H, Kirin M, Pehlic M, Faletra F, Porteous D, Pistis G, Widen E, Salomaa V, Koskinen S, Fischer K, Lehtimaki T, Heath A, McCarthy MI, Rivadeneira F, Montgomery GW, Tiemeier H, Hartikainen AL, Madden PAF, d'Adamo P, Hastie ND, Gyllensten U, Wright AF, van Duijn CM, Dunlop M, Rudan I, Gasparini P, Pramstaller PP, Deary IJ, Toniolo D, Eriksson JG, Jula A, Raitakari OT, Metspalu A, Perola M, Jarvelin MR, Uitterlinden A, Visscher PM, Wilson JF
Kustantaja: PUBLIC LIBRARY SCIENCE
Julkaisuvuosi: 2012
Journal: PLoS Genetics
Tietokannassa oleva lehden nimi: PLOS GENETICS
Lehden akronyymi: PLOS GENET
Artikkelin numero: ARTN e1002655
Numero sarjassa: 7
Vuosikerta: 8
Numero: 7
Aloitussivu: e12655
Sivujen määrä: 14
ISSN: 1553-7390
DOI: https://doi.org/10.1371/journal.pgen.1002655
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 (chi(2) = 83.89, df = 1; p = 5.2 x 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.
