Evidence of Inbreeding Depression on Human Height

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McQuillan, Ruth (author)

Evidence of Inbreeding Depression on Human Height

Article/chapterEnglish2012

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2012-07-19
Public Library of Science (PLoS),2012
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:uu-179424
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-179424URI
https://doi.org/10.1371/journal.pgen.1002655DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

Added entries (persons, corporate bodies, meetings, titles ...)

Eklund, Niina (author)
Pirastu, Nicola (author)
Kuningas, Maris (author)
McEvoy, Brian P (author)
Esko, Tõnu (author)
Corre, Tanguy (author)
Davies, Gail (author)
Kaakinen, Marika (author)
Lyytikäinen, Leo-Pekka (author)
Kristiansson, Kati (author)
Havulinna, Aki S (author)
Gögele, Martin (author)
Vitart, Veronique (author)
Tenesa, Albert (author)
Aulchenko, Yurii (author)
Hayward, Caroline (author)
Johansson, ÅsaUppsala universitet,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)asjoh108 (author)
Boban, Mladen (author)
Ulivi, Sheila (author)
Robino, Antonietta (author)
Boraska, Vesna (author)
Igl, WilmarUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab (author)
Wild, Sarah H (author)
Zgaga, Lina (author)
Amin, Najaf (author)
Theodoratou, Evropi (author)
Polašek, Ozren (author)
Girotto, Giorgia (author)
Lopez, Lorna M (author)
Sala, Cinzia (author)
Lahti, Jari (author)
Laatikainen, Tiina (author)
Prokopenko, Inga (author)
Kals, Mart (author)
Viikari, Jorma (author)
Yang, Jian (author)
Pouta, Anneli (author)
Estrada, Karol (author)
Hofman, Albert (author)
Freimer, Nelson (author)
Martin, Nicholas G (author)
Kähönen, Mika (author)
Milani, Lili (author)
Heliövaara, Markku (author)
Vartiainen, Erkki (author)
Räikkönen, Katri (author)
Masciullo, Corrado (author)
Starr, John M (author)
Hicks, Andrew A (author)
Esposito, Laura (author)
Kolčić, Ivana (author)
Farrington, Susan M (author)
Oostra, Ben (author)
Zemunik, Tatijana (author)
Campbell, Harry (author)
Kirin, Mirna (author)
Pehlic, Marina (author)
Faletra, Flavio (author)
Porteous, David (author)
Pistis, Giorgio (author)
Widén, Elisabeth (author)
Salomaa, Veikko (author)
Koskinen, Seppo (author)
Fischer, Krista (author)
Lehtimäki, Terho (author)
Heath, Andrew (author)
McCarthy, Mark I (author)
Rivadeneira, Fernando (author)
Montgomery, Grant W (author)
Tiemeier, Henning (author)
Hartikainen, Anna-Liisa (author)
Madden, Pamela A F (author)
d'Adamo, Pio (author)
Hastie, Nicholas D (author)
Gyllensten, UlfUppsala universitet,Genomik,Science for Life Laboratory, SciLifeLab(Swepub:uu)ulfgyll (author)
Wright, Alan F (author)
van Duijn, Cornelia M (author)
Dunlop, Malcolm (author)
Rudan, Igor (author)
Gasparini, Paolo (author)
Pramstaller, Peter P (author)
Deary, Ian J (author)
Toniolo, Daniela (author)
Eriksson, Johan G (author)
Jula, Antti (author)
Raitakari, Olli T (author)
Metspalu, Andres (author)
Perola, Markus (author)
Järvelin, Marjo-Riitta (author)
Uitterlinden, André (author)
Visscher, Peter M (author)
Wilson, James F (author)
Uppsala universitetUppsala kliniska forskningscentrum (UCR) (creator_code:org_t)

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In:PLOS Genetics: Public Library of Science (PLoS)8:7, s. e1002655-1553-7404

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By the author/editor: McQuillan, Ruth; Eklund, Niina; Pirastu, Nicola; Kuningas, Maris; McEvoy, Brian P; Esko, Tõnu; show more...; Corre, Tanguy; Davies, Gail; Kaakinen, Marika; Lyytikäinen, Leo ...; Kristiansson, Ka ...; Havulinna, Aki S; Gögele, Martin; Vitart, Veroniqu ...; Tenesa, Albert; Aulchenko, Yurii; Hayward, Carolin ...; Johansson, Åsa; Boban, Mladen; Ulivi, Sheila; Robino, Antoniet ...; Boraska, Vesna; Igl, Wilmar; Wild, Sarah H; Zgaga, Lina; Amin, Najaf; Theodoratou, Evr ...; Polašek, Ozren; Girotto, Giorgia; Lopez, Lorna M; Sala, Cinzia; Lahti, Jari; Laatikainen, Tii ...; Prokopenko, Inga; Kals, Mart; Viikari, Jorma; Yang, Jian; Pouta, Anneli; Estrada, Karol; Hofman, Albert; Freimer, Nelson; Martin, Nicholas ...; Kähönen, Mika; Milani, Lili; Heliövaara, Mark ...; Vartiainen, Erkk ...; Räikkönen, Katri; Masciullo, Corra ...; Starr, John M; Hicks, Andrew A; Esposito, Laura; Kolčić, Ivana; Farrington, Susa ...; Oostra, Ben; Zemunik, Tatijan ...; 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, Fer ...; Montgomery, Gran ...; Tiemeier, Hennin ...; Hartikainen, Ann ...; Madden, Pamela A ...; d'Adamo, Pio; Hastie, Nicholas ...; Gyllensten, Ulf; Wright, Alan F; van Duijn, Corne ...; Dunlop, Malcolm; Rudan, Igor; Gasparini, Paolo; Pramstaller, Pet ...; Deary, Ian J; Toniolo, Daniela; Eriksson, Johan ...; Jula, Antti; Raitakari, Olli ...; Metspalu, Andres; Perola, Markus; Järvelin, Marjo- ...; Uitterlinden, An ...; Visscher, Peter ...; Wilson, James F; show less...

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