Evidence of inbreeding depression on human height

McQuillan, Ruth, Eklund, Niina, Pirastu, Nicola, Kuningas, Maris, McEvoy, Brian P., Esko, Tonu, Corre, Tanguy, Davies, Gail, Kaakinen, Marika, Lyytikainen, Leo-Pekka, Kristiansson, Kati, Havulinna, Aki S., Gogele, Martin, Vitart, Veronique, Tenesa, Albert, Aulchenko, Yurii, Hayward, Caroline, Johansson, Asa, Boban, Mladen, Ulivi, Sheila, Robino, Antonietta, Boraska, Vesna, Igl, Wilmar, Wild, Sarah H., Zgaga, Lina, Amin, Najaf, Theodoratou, Evropi, Polasek, 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., Kahonen, Mika, Milani, Lili, Heliovaara, Markku, Vartiainen, Erkki, Raikkonen, Katri, Masciullo, Corrado, Starr, John M., Hicks, Andrew A., Esposito, Laura, Kolcic, Ivana, Farrington, Susan M., Oostra, Ben, Zemunik, Tatijana, Campbell, Harry, Kirin, Mirna, Pehlic, Marina, Faletra, Flavio, Porteous, David, Pistis, Giorgio, Widen, Elisabeth, Salomaa, Veikko, Koskinen, Seppo, Fischer, Krista, Lehtimaki, 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, Jarvelin, Marjo-Riitta, Uitterlinden, Andre, Visscher, Peter M. and Wilson, James F. (2012) Evidence of inbreeding depression on human height. Plos Genetics, 8 7: . doi:10.1371/journal.pgen.1002655


Author McQuillan, Ruth
Eklund, Niina
Pirastu, Nicola
Kuningas, Maris
McEvoy, Brian P.
Esko, Tonu
Corre, Tanguy
Davies, Gail
Kaakinen, Marika
Lyytikainen, Leo-Pekka
Kristiansson, Kati
Havulinna, Aki S.
Gogele, Martin
Vitart, Veronique
Tenesa, Albert
Aulchenko, Yurii
Hayward, Caroline
Johansson, Asa
Boban, Mladen
Ulivi, Sheila
Robino, Antonietta
Boraska, Vesna
Igl, Wilmar
Wild, Sarah H.
Zgaga, Lina
Amin, Najaf
Theodoratou, Evropi
Polasek, 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.
Kahonen, Mika
Milani, Lili
Heliovaara, Markku
Vartiainen, Erkki
Raikkonen, Katri
Masciullo, Corrado
Starr, John M.
Hicks, Andrew A.
Esposito, Laura
Kolcic, Ivana
Farrington, Susan M.
Oostra, Ben
Zemunik, Tatijana
Campbell, Harry
Kirin, Mirna
Pehlic, Marina
Faletra, Flavio
Porteous, David
Pistis, Giorgio
Widen, Elisabeth
Salomaa, Veikko
Koskinen, Seppo
Fischer, Krista
Lehtimaki, 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
Jarvelin, Marjo-Riitta
Uitterlinden, Andre
Visscher, Peter M.
Wilson, James F.
Title Evidence of inbreeding depression on human height
Journal name Plos Genetics   Check publisher's open access policy
ISSN 1553-7404
1553-7390
Publication date 2012-07
Year available 2012
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1002655
Open Access Status DOI
Volume 8
Issue 7
Total pages 14
Place of publication San Francisco, United States
Publisher Public Library of Science (PLoS)
Language eng
Formatted 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 (χ2 = 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.
Keyword Wide association analysis
Coronary-heart-disease
British womens heart
Quantitative traits
Adult height
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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