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    Evidence of Inbreeding Depression on Human Height


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    Gibson, Greg, McQuillan, Ruth, Eklund, Niina, Pirastu, Nicola, Kuningas, Maris, McEvoy, Brian P., Esko, Tõnu, Corre, Tanguy, Davies, Gail, Kaakinen, Marika, Lyytikäinen, Leo-Pekka, Kristiansson, Kati, Havulinna, Aki S., Gögele, Martin, Vitart, Veronique, Tenesa, Albert, Aulchenko, Yurii, Hayward, Caroline, Johansson, Åsa, Boban, Mladen, Ulivi, Sheila, Robino, Antonietta, Boraska, Vesna, Igl, Wilmar, Wild, Sarah H., Zgaga, Lina, Amin, Najaf, Theodoratou, Evropi, Polašek, Ozren, Girotto, Giorgia, Lopez, Lorna M., Sala, Cinzia, Lahti, Jari, Laatikainen, Tiina, Prokopenko, Inga, Kals, Mart, Viikari, Jorma, Yang, Jian, Pouta, Anneli, Estrada, Karol, Hofman, Albert, Freimer, Nelson, Martin, Nicholas G., Kähönen, Mika, Milani, Lili, Heliövaara, Markku, Vartiainen, Erkki, Räikkönen, Katri, Masciullo, Corrado, Starr, John M., Hicks, Andrew A., Esposito, Laura, Kolčić, Ivana, Farrington, Susan M., Oostra, Ben, Zemunik, Tatijana, Campbell, Harry, Kirin, Mirna, Pehlic, Marina, Faletra, Flavio, Porteous, David, Pistis, Giorgio, Widén, Elisabeth, Salomaa, Veikko, Koskinen, Seppo, Fischer, Krista, Lehtimäki, Terho, Heath, Andrew, McCarthy, Mark I., Rivadeneira, Fernando, Montgomery, Grant W., Tiemeier, Henning, Hartikainen, Anna-Liisa, Madden, Pamela A. F., d'Adamo, Pio, Hastie, Nicholas D., Gyllensten, Ulf, Wright, Alan F., van Duijn, Cornelia M., Dunlop, Malcolm, Rudan, Igor, Gasparini, Paolo, Pramstaller, Peter P., Deary, Ian J., Toniolo, Daniela, Eriksson, Johan G., Jula, Antti, Raitakari, Olli T., Metspalu, Andres, Perola, Markus, Järvelin, Marjo-Riitta, Uitterlinden, André, Visscher, Peter M. and Wilson, James F. (2012) Evidence of Inbreeding Depression on Human Height. PLoS Genetics, 8 (7). pp. 1-15. ISSN 1553-7404

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    Abstract

    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.
    Item Type: Article
    Keywords: evidence; inbreeding; depression; human height;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 17394
    Identification Number: 10.1371/journal.pgen.1002655
    Depositing User: Lorna Lopez
    Date Deposited: 10 Jul 2023 13:52
    Journal or Publication Title: PLoS Genetics
    Publisher: Elsevier
    Refereed: Yes
    Related URLs:
    URI: https://mural.maynoothuniversity.ie/id/eprint/17394
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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