TY - JOUR
T1 - Evidence of inbreeding depression on human height.
JF - PLoS Genet
Y1 - 2012
A1 - McQuillan, Ruth
A1 - Eklund, Niina
A1 - Pirastu, Nicola
A1 - Kuningas, Maris
A1 - McEvoy, Brian P
A1 - Esko, Tõnu
A1 - Corre, Tanguy
A1 - Davies, Gail
A1 - Kaakinen, Marika
A1 - Lyytikäinen, Leo-Pekka
A1 - Kristiansson, Kati
A1 - Havulinna, Aki S
A1 - Gögele, Martin
A1 - Vitart, Veronique
A1 - Tenesa, Albert
A1 - Aulchenko, Yurii
A1 - Hayward, Caroline
A1 - Johansson, Åsa
A1 - Boban, Mladen
A1 - Ulivi, Sheila
A1 - Robino, Antonietta
A1 - Boraska, Vesna
A1 - Igl, Wilmar
A1 - Wild, Sarah H
A1 - Zgaga, Lina
A1 - Amin, Najaf
A1 - Theodoratou, Evropi
A1 - Polasek, Ozren
A1 - Girotto, Giorgia
A1 - Lopez, Lorna M
A1 - Sala, Cinzia
A1 - Lahti, Jari
A1 - Laatikainen, Tiina
A1 - Prokopenko, Inga
A1 - Kals, Mart
A1 - Viikari, Jorma
A1 - Yang, Jian
A1 - Pouta, Anneli
A1 - Estrada, Karol
A1 - Hofman, Albert
A1 - Freimer, Nelson
A1 - Martin, Nicholas G
A1 - Kähönen, Mika
A1 - Milani, Lili
A1 - Heliövaara, Markku
A1 - Vartiainen, Erkki
A1 - Räikkönen, Katri
A1 - Masciullo, Corrado
A1 - Starr, John M
A1 - Hicks, Andrew A
A1 - Esposito, Laura
A1 - Kolcic, Ivana
A1 - Farrington, Susan M
A1 - Oostra, Ben
A1 - Zemunik, Tatijana
A1 - Campbell, Harry
A1 - Kirin, Mirna
A1 - Pehlic, Marina
A1 - Faletra, Flavio
A1 - Porteous, David
A1 - Pistis, Giorgio
A1 - Widen, Elisabeth
A1 - Salomaa, Veikko
A1 - Koskinen, Seppo
A1 - Fischer, Krista
A1 - Lehtimäki, Terho
A1 - Heath, Andrew
A1 - McCarthy, Mark I
A1 - Rivadeneira, Fernando
A1 - Montgomery, Grant W
A1 - Tiemeier, Henning
A1 - Hartikainen, Anna-Liisa
A1 - Madden, Pamela A F
A1 - d'Adamo, Pio
A1 - Hastie, Nicholas D
A1 - Gyllensten, Ulf
A1 - Wright, Alan F
A1 - van Duijn, Cornelia M
A1 - Dunlop, Malcolm
A1 - Rudan, Igor
A1 - Gasparini, Paolo
A1 - Pramstaller, Peter P
A1 - Deary, Ian J
A1 - Toniolo, Daniela
A1 - Eriksson, Johan G
A1 - Jula, Antti
A1 - Raitakari, Olli T
A1 - Metspalu, Andres
A1 - Perola, Markus
A1 - Järvelin, Marjo-Riitta
A1 - Uitterlinden, André
A1 - Visscher, Peter M
A1 - Wilson, James F
KW - Adult
KW - Aged
KW - Body Height
KW - Consanguinity
KW - Databases, Genetic
KW - Family
KW - Female
KW - Genes, Recessive
KW - Genetic Heterogeneity
KW - Genome-Wide Association Study
KW - Homozygote
KW - Humans
KW - Male
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Quantitative Trait, Heritable
AB - 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 (χ(2) = 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.

VL - 8
IS - 7
U1 - http://www.ncbi.nlm.nih.gov/pubmed/22829771?dopt=Abstract
ER -