Directional dominance on stature and cognition in diverse human populations.

Joshi, P.K.; Esko, T.; Mattsson, H.; Eklund, N.; Gandin, I.; Nutile, T.; Jackson, A.U.; Schurmann, C.; Smith, A.V.; Zhang, W.; Okada, Y.; Stančáková, A.; Faul, J.D.; Zhao, W.; Bartz, T.M.; Concas, M.P.; Franceschini, N.; Enroth, S.; Vitart, V.; Trompet, S.; Guo, X.; Chasman, D.I.; O'Connel, J.R.; Corre, T.; Nongmaithem, S.S.; Chen, Y.; Mangino, M.; Ruggiero, D.; Traglia, M.; Farmaki, A.E.; Kacprowski, T.; Bjonnes, A.; van der Spek, A.; Wu, Y.; Giri, A.K.; Yanek, L.R.; Wang, L.; Hofer, E.; Rietveld, C.A.; McLeod, O.; Cornelis, M.C.; Pattaro, C.; Verweij, N.; Baumbach, C.; Abdellaoui, A.; Warren, H.R.; Vuckovic, D.; Mei, H.; Bouchard, C.; Perry, J.R.; Cappellani, S.; Mirza, S.S.; Benton, M.C.; Broeckel, U.; Medland, S.E.; Lind, P.A.; Malerba, G.; Drong, A.; Yengo, L.; Bielak, L.F.; Zhi, D.; van der Most, P.J.; Shriner, D.; Mägi, R.; Hemani, G.; Karaderi, T.; Wang, Z.; Liu, T.; Demuth, I.; Zhao, J.H.; Meng, W.; Lataniotis, L.; van der Laan, S.W.; Bradfield, J.P.; Wood, A.R.; Bonnefond, A.; Ahluwalia, T.S.; Hall, L.M.; Salvi, E.; Yazar, S.; Carstensen, L.; de Haan, H.G.; Abney, M.; Afzal, U.; Allison, M.A.; Amin, N.; Asselbergs, F.W.; Bakker, S.J.; Barr, R.G.; Baumeister, S.E.; Benjamin, D.J.; Bergmann, S.; Boerwinkle, E.; Bottinger, E.P.; Campbell, A.; Chakravarti, A.; Chan, Y.; Chanock, S.J.; Chen, C.; Chen, Y.D.; Collins, F.S.; Connell, J.; Correa, A.; Cupples, L.A.; Smith, G.D.; Davies, G.; Dörr, M.; Ehret, G.; Ellis, S.B.; Feenstra, B.; Feitosa, M.F.; Ford, I.; Fox, C.S.; Frayling, T.M.; Friedrich, N.; Geller, F.; Scotland, G.; Gillham-Nasenya, I.; Gottesman, O.; Graff, M.; Grodstein, F.; Gu, C.; Haley, C.; Hammond, C.J.; Harris, S.E.; Harris, T.B.; Hastie, N.D.; Heard-Costa, N.L.; Heikkilä, K.; Hocking, L.J.; Homuth, G.; Hottenga, J.J.; Huang, J.; Huffman, J.E.; Hysi, P.G.; Ikram, M.A.; Ingelsson, E.; Joensuu, A.; Johansson, Å.; Jousilahti, P.; Jukema, J.W.; Kähönen, M.; Kamatani, Y.; Kanoni, S.; Kerr, S.M.; Khan, N.M.; Koellinger, P.; Koistinen, H.A.; Kooner, M.K.; Kubo, M.; Kuusisto, J.; Lahti, J.; Launer, L.J.; Lea, R.A.; Lehne, B.; Lehtimäki, T.; Liewald, D.C.; Lind, L.; Loh, M.; Lokki, M.L.; London, S.J.; Loomis, S.J.; Loukola, A.; Lu, Y.; Lumley, T.; Lundqvist, A.; Männistö, S.; Marques-Vidal, P.; Masciullo, C.; Matchan, A.; Mathias, R.A.; Matsuda, K.; Meigs, J.B.; Meisinger, C.; Meitinger, T.; Menni, C.; Mentch, F.D.; Mihailov, E.; Milani, L.; Montasser, M.E.; Montgomery, G.W.; Morrison, A.; Myers, R.H.; Nadukuru, R.; Navarro, P.; Nelis, M.; Nieminen, M.S.; Nolte, I.M.; O'Connor, G.T.; Ogunniyi, A.; Padmanabhan, S.; Palmas, W.R.; Pankow, J.S.; Patarcic, I.; Pavani, F.; Peyser, P.A.; Pietilainen, K.; Poulter, N.; Prokopenko, I.; Ralhan, S.; Redmond, P.; Rich, S.S.; Rissanen, H.; Robino, A.; Rose, L.M.; Rose, R.; Sala, C.; Salako, B.; Salomaa, V.; Sarin, A.P.; Saxena, R.; Schmidt, H.; Scott, L.J.; Scott, W.R.; Sennblad, B.; Seshadri, S.; Sever, P.; Shrestha, S.; Smith, B.H.; Smith, J.A.; Soranzo, N.; Sotoodehnia, N.; Southam, L.; Stanton, A.V.; Stathopoulou, M.G.; Strauch, K.; Strawbridge, R.J.; Suderman, M.J.; Tandon, N.; Tang, S.T.; Taylor, K.D.; Tayo, B.O.; Töglhofer, A.M.; Tomaszewski, M.; T?ernikova N.,; Tuomilehto, J.; Uitterlinden, A.G.; Vaidya, D.; van Hylckama Vlieg, A.; van Setten, J.; Vasankari, T.; Vedantam, S.; Vlachopoulou, E.; Vozzi, D.; Vuoksimaa, E.; Waldenberger, M.; Ware, E.B.; Wentworth-Shields, W.; Whitfield, J.B.; Wild, S.; Willemsen, G.; Yajnik, C.S.; Yao, J.; Zaza, G.; Zhu, X.; BioBank Japan, Project; Salem, R.M.; Salem, R.M.; Melbye, M.; Bisgaard, H.; Samani, N.J.; Cusi, D.; Mackey, D.A.; Cooper, R.S.; Froguel, P.; Pasterkamp, G.; Grant, S.F.; Hakonarson, H.; Ferrucci, L.; Scott, R.A.; Morris, A.D.; Palmer, C.N.; Dedoussis, G.; Deloukas, P.; Bertram, L.; Lindenberger, U.; Berndt, S.I.; Lindgren, C.M.; Timpson, N.J.; Tönjes, A.; Munroe, P.B.; Sørensen, T.I.; Rotimi, C.N.; Arnett, D.K.; Oldehinkel, A.J.; Kardia, S.L.; Balkau, B.; Gambaro, G.; Morris, A.P.; Eriksson, J.G.; Wright, M.J.; Martin, N.G.; Hunt, S.C.; Starr, J.M.; Deary, I.J.; Griffiths, L.R.; Tiemeier, H.; Pirastu, N.; Kaprio, J.; Wareham, N.J.; Pérusse, L.; Wilson, J.G.; Girotto, G.; Caulfield, M.J.; Raitakari, O.; Boomsma, D.I.; Gieger, C.; van der Harst, P.; Hicks, A.A.; Kraft, P.; Sinisalo, J.; Knekt, P.; Johannesson, M.; Magnusson, P.K.; Hamsten, A.; Schmidt, R.; Borecki, I.B.; Vartiainen, E.; Becker, D.M.; Bharadwaj, D.; Mohlke, K.L.; Boehnke, M.; van Duijn, C.M.; Sanghera, D.K.; Teumer, A.; Zeggini, E.; Metspalu, A.; Gasparini, P.; Ulivi, S.; Ober, C.; Toniolo, D.; Rudan, I.; Porteous, D.J.; Ciullo, M.; Spector, T.D.; Hayward, C.; Dupuis, J.; Loos, R.J.; Wright, A.F.; Chandak, G.R.; Vollenweider, P.; Shuldiner, A.R.; Ridker, P.M.; Rotter, J.I.; Sattar, N.; Gyllensten, U.; North, K.E.; Pirastu, M.; Psaty, B.M.; Weir, D.R.; Laakso, M.; Gudnason, V.; Takahashi, A.; Chambers, J.C.; Kooner, J.S.; Strachan, D.P.; Campbell, H.; Hirschhorn, J.N.; Perola, M.; Pola?ek O.,; Wilson, J.F.

doi:10.1038/nature14618

Directional dominance on stature and cognition in diverse human populations.

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Download: BIB_E6FE1E6B0AA3.P001.pdf (2946.55 [Ko])
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Serval ID

serval:BIB_E6FE1E6B0AA3

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Directional dominance on stature and cognition in diverse human populations.

Journal

Nature

Author(s)

Joshi P.K., Esko T., Mattsson H., Eklund N., Gandin I., Nutile T., Jackson A.U., Schurmann C., Smith A.V., Zhang W., Okada Y., Stančáková A., Faul J.D., Zhao W., Bartz T.M., Concas M.P., Franceschini N., Enroth S., Vitart V., Trompet S., Guo X., Chasman D.I., O'Connel J.R., Corre T., Nongmaithem S.S., Chen Y., Mangino M., Ruggiero D., Traglia M., Farmaki A.E., Kacprowski T., Bjonnes A., van der Spek A., Wu Y., Giri A.K., Yanek L.R., Wang L., Hofer E., Rietveld C.A., McLeod O., Cornelis M.C., Pattaro C., Verweij N., Baumbach C., Abdellaoui A., Warren H.R., Vuckovic D., Mei H., Bouchard C., Perry J.R., Cappellani S., Mirza S.S., Benton M.C., Broeckel U., Medland S.E., Lind P.A., Malerba G., Drong A., Yengo L., Bielak L.F., Zhi D., van der Most P.J., Shriner D., Mägi R., Hemani G., Karaderi T., Wang Z., Liu T., Demuth I., Zhao J.H., Meng W., Lataniotis L., van der Laan S.W., Bradfield J.P., Wood A.R., Bonnefond A., Ahluwalia T.S., Hall L.M., Salvi E., Yazar S., Carstensen L., de Haan H.G., Abney M., Afzal U., Allison M.A., Amin N., Asselbergs F.W., Bakker S.J., Barr R.G., Baumeister S.E., Benjamin D.J., Bergmann S., Boerwinkle E., Bottinger E.P., Campbell A., Chakravarti A., Chan Y., Chanock S.J., Chen C., Chen Y.D., Collins F.S., Connell J., Correa A., Cupples L.A., Smith G.D., Davies G., Dörr M., Ehret G., Ellis S.B., Feenstra B., Feitosa M.F., Ford I., Fox C.S., Frayling T.M., Friedrich N., Geller F., Scotland G., Gillham-Nasenya I., Gottesman O., Graff M., Grodstein F., Gu C., Haley C., Hammond C.J., Harris S.E., Harris T.B., Hastie N.D., Heard-Costa N.L., Heikkilä K., Hocking L.J., Homuth G., Hottenga J.J., Huang J., Huffman J.E., Hysi P.G., Ikram M.A., Ingelsson E., Joensuu A., Johansson Å., Jousilahti P., Jukema J.W., Kähönen M., Kamatani Y., Kanoni S., Kerr S.M., Khan N.M., Koellinger P., Koistinen H.A., Kooner M.K., Kubo M., Kuusisto J., Lahti J., Launer L.J., Lea R.A., Lehne B., Lehtimäki T., Liewald D.C., Lind L., Loh M., Lokki M.L., London S.J., Loomis S.J., Loukola A., Lu Y., Lumley T., Lundqvist A., Männistö S., Marques-Vidal P., Masciullo C., Matchan A., Mathias R.A., Matsuda K., Meigs J.B., Meisinger C., Meitinger T., Menni C., Mentch F.D., Mihailov E., Milani L., Montasser M.E., Montgomery G.W., Morrison A., Myers R.H., Nadukuru R., Navarro P., Nelis M., Nieminen M.S., Nolte I.M., O'Connor G.T., Ogunniyi A., Padmanabhan S., Palmas W.R., Pankow J.S., Patarcic I., Pavani F., Peyser P.A., Pietilainen K., Poulter N., Prokopenko I., Ralhan S., Redmond P., Rich S.S., Rissanen H., Robino A., Rose L.M., Rose R., Sala C., Salako B., Salomaa V., Sarin A.P., Saxena R., Schmidt H., Scott L.J., Scott W.R., Sennblad B., Seshadri S., Sever P., Shrestha S., Smith B.H., Smith J.A., Soranzo N., Sotoodehnia N., Southam L., Stanton A.V., Stathopoulou M.G., Strauch K., Strawbridge R.J., Suderman M.J., Tandon N., Tang S.T., Taylor K.D., Tayo B.O., Töglhofer A.M., Tomaszewski M., T?ernikova N. , Tuomilehto J., Uitterlinden A.G., Vaidya D., van Hylckama Vlieg A., van Setten J., Vasankari T., Vedantam S., Vlachopoulou E., Vozzi D., Vuoksimaa E., Waldenberger M., Ware E.B., Wentworth-Shields W., Whitfield J.B., Wild S., Willemsen G., Yajnik C.S., Yao J., Zaza G., Zhu X., BioBank Japan Project, Salem R.M., Salem R.M., Melbye M., Bisgaard H., Samani N.J., Cusi D., Mackey D.A., Cooper R.S., Froguel P., Pasterkamp G., Grant S.F., Hakonarson H., Ferrucci L., Scott R.A., Morris A.D., Palmer C.N., Dedoussis G., Deloukas P., Bertram L., Lindenberger U., Berndt S.I., Lindgren C.M., Timpson N.J., Tönjes A., Munroe P.B., Sørensen T.I., Rotimi C.N., Arnett D.K., Oldehinkel A.J., Kardia S.L., Balkau B., Gambaro G., Morris A.P., Eriksson J.G., Wright M.J., Martin N.G., Hunt S.C., Starr J.M., Deary I.J., Griffiths L.R., Tiemeier H., Pirastu N., Kaprio J., Wareham N.J., Pérusse L., Wilson J.G., Girotto G., Caulfield M.J., Raitakari O., Boomsma D.I., Gieger C., van der Harst P., Hicks A.A., Kraft P., Sinisalo J., Knekt P., Johannesson M., Magnusson P.K., Hamsten A., Schmidt R., Borecki I.B., Vartiainen E., Becker D.M., Bharadwaj D., Mohlke K.L., Boehnke M., van Duijn C.M., Sanghera D.K., Teumer A., Zeggini E., Metspalu A., Gasparini P., Ulivi S., Ober C., Toniolo D., Rudan I., Porteous D.J., Ciullo M., Spector T.D., Hayward C., Dupuis J., Loos R.J., Wright A.F., Chandak G.R., Vollenweider P., Shuldiner A.R., Ridker P.M., Rotter J.I., Sattar N., Gyllensten U., North K.E., Pirastu M., Psaty B.M., Weir D.R., Laakso M., Gudnason V., Takahashi A., Chambers J.C., Kooner J.S., Strachan D.P., Campbell H., Hirschhorn J.N., Perola M., Pola?ek O. , Wilson J.F.

Contributor(s)

BioBank Japan Project

ISSN

1476-4687 (Electronic)

ISSN-L

0028-0836

Publication state

Published

Issued date

2015

Peer-reviewed

Oui

Volume

523

Number

7561

Pages

459-462

Language

english

Notes

Publication types: Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov'tPublication Status: ppublish

Abstract

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Keywords

Biological Evolution, Blood Pressure/genetics, Body Height/genetics, Cholesterol, LDL/genetics, Cognition, Cohort Studies, Educational Status, Female, Forced Expiratory Volume/genetics, Genome, Human/genetics, Homozygote, Humans, Lung Volume Measurements, Male, Phenotype

URN

urn:nbn:ch:serval-BIB_E6FE1E6B0AA33

OAI-PMH

oai:serval.unil.ch:BIB_E6FE1E6B0AA3

DOI

10.1038/nature14618

Pubmed

26131930

Web of science

000358378900036

Create date

27/08/2015 10:39