Directional dominance on stature and cognition in diverse human populations

P.K. Joshi; T. Esko; H. Mattsson; N. Eklund; I. Gandin; T. Nutile; A.U. Jackson; C. Schurmann; A.V. Smith; W. Zhang; Y. Okada; A. Stančáková; J.D. Faul; W. Zhao; T.M. Bartz; M.P. Concas; N. Franceschini; S. Enroth; V. Vitart; S. Trompet; X. Guo; D.I. Chasman; J.R. O'Connel; T. Corre; S.S. Nongmaithem; Y. Chen; M. Mangino; D. Ruggiero; M. Traglia; A.E. Farmaki; T. Kacprowski; A. Bjonnes; A. Van Der Spek; Y. Wu; A.K. Giri; L.R. Yanek; L. Wang; E. Hofer; C.A. Rietveld; O. Mcleod; M.C. Cornelis; C. Pattaro; N. Verweij; C. Baumbach; A. Abdellaoui; H.R. Warren; D. Vuckovic; H. Mei; C. Bouchard; J.R.B. Perry; S. Cappellani; S.S. Mirza; M.C. Benton; U. Broeckel; S.E. Medland; P.A. Lind; G. Malerba; A. Drong; L. Yengo; L.F. Bielak; D. Zhi; P.J. Van Der Most; D. Shriner; R. Mägi; G. Hemani; T. Karaderi; Z. Wang; T. Liu; I. Demuth; J.H. Zhao; W. Meng; L. Lataniotis; S.W. Van Der Laan; J.P. Bradfield; A.R. Wood; A. Bonnefond; T.S. Ahluwalia; L.M. Hall; Seyhan Yazar; David Mackey

doi:10.1038/nature14618

Directional dominance on stature and cognition in diverse human populations

P.K. Joshi, T. Esko, H. Mattsson, N. Eklund, I. Gandin, T. Nutile, A.U. Jackson, C. Schurmann, A.V. Smith, W. Zhang, Y. Okada, A. Stančáková, J.D. Faul, W. Zhao, T.M. Bartz, M.P. Concas, N. Franceschini, S. Enroth, V. Vitart, S. TrompetX. Guo, D.I. Chasman, J.R. O'Connel, T. Corre, S.S. Nongmaithem, Y. Chen, M. Mangino, D. Ruggiero, M. Traglia, A.E. Farmaki, T. Kacprowski, A. Bjonnes, A. Van Der Spek, Y. Wu, A.K. Giri, L.R. Yanek, L. Wang, E. Hofer, C.A. Rietveld, O. Mcleod, M.C. Cornelis, C. Pattaro, N. Verweij, C. Baumbach, A. Abdellaoui, H.R. Warren, D. Vuckovic, H. Mei, C. Bouchard, J.R.B. Perry, S. Cappellani, S.S. Mirza, M.C. Benton, U. Broeckel, S.E. Medland, P.A. Lind, G. Malerba, A. Drong, L. Yengo, L.F. Bielak, D. Zhi, P.J. Van Der Most, D. Shriner, R. Mägi, G. Hemani, T. Karaderi, Z. Wang, T. Liu, I. Demuth, J.H. Zhao, W. Meng, L. Lataniotis, S.W. Van Der Laan, J.P. Bradfield, A.R. Wood, A. Bonnefond, T.S. Ahluwalia, L.M. Hall, Seyhan Yazar, David Mackey

Research output: Contribution to journal › Article › peer-review

134 Citations (Scopus)

Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. 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.

Original language	English
Pages (from-to)	459-462
Journal	Nature
Volume	523
Issue number	7561
DOIs	https://doi.org/10.1038/nature14618
Publication status	Published - 2015

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nature14618

Cite this

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., ... Mackey, D. (2015). Directional dominance on stature and cognition in diverse human populations. Nature, 523(7561), 459-462. https://doi.org/10.1038/nature14618

@article{3a37420b8e324cdd952233683b5d7bf1,

title = "Directional dominance on stature and cognition in diverse human populations",

abstract = "{\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved. 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.",

author = "P.K. Joshi and T. Esko and H. Mattsson and N. Eklund and I. Gandin and T. Nutile and A.U. Jackson and C. Schurmann and A.V. Smith and W. Zhang and Y. Okada and A. Stan{\v c}{\'a}kov{\'a} and J.D. Faul and W. Zhao and T.M. Bartz and M.P. Concas and N. Franceschini and S. Enroth and V. Vitart and S. Trompet and X. Guo and D.I. Chasman and J.R. O'Connel and T. Corre and S.S. Nongmaithem and Y. Chen and M. Mangino and D. Ruggiero and M. Traglia and A.E. Farmaki and T. Kacprowski and A. Bjonnes and {Van Der Spek}, A. and Y. Wu and A.K. Giri and L.R. Yanek and L. Wang and E. Hofer and C.A. Rietveld and O. Mcleod and M.C. Cornelis and C. Pattaro and N. Verweij and C. Baumbach and A. Abdellaoui and H.R. Warren and D. Vuckovic and H. Mei and C. Bouchard and J.R.B. Perry and S. Cappellani and S.S. Mirza and M.C. Benton and U. Broeckel and S.E. Medland and P.A. Lind and G. Malerba and A. Drong and L. Yengo and L.F. Bielak and D. Zhi and {Van Der Most}, P.J. and D. Shriner and R. M{\"a}gi and G. Hemani and T. Karaderi and Z. Wang and T. Liu and I. Demuth and J.H. Zhao and W. Meng and L. Lataniotis and {Van Der Laan}, S.W. and J.P. Bradfield and A.R. Wood and A. Bonnefond and T.S. Ahluwalia and L.M. Hall and Seyhan Yazar and David Mackey",

year = "2015",

doi = "10.1038/nature14618",

language = "English",

volume = "523",

pages = "459--462",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group - Macmillan Publishers",

number = "7561",

}

Joshi, PK, Esko, T, Mattsson, H, Eklund, N, Gandin, I, Nutile, T, Jackson, AU, Schurmann, C, Smith, AV, Zhang, W, Okada, Y, Stančáková, A, Faul, JD, Zhao, W, Bartz, TM, Concas, MP, Franceschini, N, Enroth, S, Vitart, V, Trompet, S, Guo, X, Chasman, DI, O'Connel, JR, Corre, T, Nongmaithem, SS, Chen, Y, Mangino, M, Ruggiero, D, Traglia, M, Farmaki, AE, Kacprowski, T, Bjonnes, A, Van Der Spek, A, Wu, Y, Giri, AK, Yanek, LR, Wang, L, Hofer, E, Rietveld, CA, Mcleod, O, Cornelis, MC, Pattaro, C, Verweij, N, Baumbach, C, Abdellaoui, A, Warren, HR, Vuckovic, D, Mei, H, Bouchard, C, Perry, JRB, Cappellani, S, Mirza, SS, Benton, MC, Broeckel, U, Medland, SE, Lind, PA, Malerba, G, Drong, A, Yengo, L, Bielak, LF, Zhi, D, Van Der Most, PJ, Shriner, D, Mägi, R, Hemani, G, Karaderi, T, Wang, Z, Liu, T, Demuth, I, Zhao, JH, Meng, W, Lataniotis, L, Van Der Laan, SW, Bradfield, JP, Wood, AR, Bonnefond, A, Ahluwalia, TS, Hall, LM, Yazar, S & Mackey, D 2015, 'Directional dominance on stature and cognition in diverse human populations', Nature, vol. 523, no. 7561, pp. 459-462. https://doi.org/10.1038/nature14618

TY - JOUR

T1 - Directional dominance on stature and cognition in diverse human populations

AU - Joshi, P.K.

AU - Esko, T.

AU - Mattsson, H.

AU - Eklund, N.

AU - Gandin, I.

AU - Nutile, T.

AU - Jackson, A.U.

AU - Schurmann, C.

AU - Smith, A.V.

AU - Zhang, W.

AU - Okada, Y.

AU - Stančáková, A.

AU - Faul, J.D.

AU - Zhao, W.

AU - Bartz, T.M.

AU - Concas, M.P.

AU - Franceschini, N.

AU - Enroth, S.

AU - Vitart, V.

AU - Trompet, S.

AU - Guo, X.

AU - Chasman, D.I.

AU - O'Connel, J.R.

AU - Corre, T.

AU - Nongmaithem, S.S.

AU - Chen, Y.

AU - Mangino, M.

AU - Ruggiero, D.

AU - Traglia, M.

AU - Farmaki, A.E.

AU - Kacprowski, T.

AU - Bjonnes, A.

AU - Van Der Spek, A.

AU - Wu, Y.

AU - Giri, A.K.

AU - Yanek, L.R.

AU - Wang, L.

AU - Hofer, E.

AU - Rietveld, C.A.

AU - Mcleod, O.

AU - Cornelis, M.C.

AU - Pattaro, C.

AU - Verweij, N.

AU - Baumbach, C.

AU - Abdellaoui, A.

AU - Warren, H.R.

AU - Vuckovic, D.

AU - Mei, H.

AU - Bouchard, C.

AU - Perry, J.R.B.

AU - Cappellani, S.

AU - Mirza, S.S.

AU - Benton, M.C.

AU - Broeckel, U.

AU - Medland, S.E.

AU - Lind, P.A.

AU - Malerba, G.

AU - Drong, A.

AU - Yengo, L.

AU - Bielak, L.F.

AU - Zhi, D.

AU - Van Der Most, P.J.

AU - Shriner, D.

AU - Mägi, R.

AU - Hemani, G.

AU - Karaderi, T.

AU - Wang, Z.

AU - Liu, T.

AU - Demuth, I.

AU - Zhao, J.H.

AU - Meng, W.

AU - Lataniotis, L.

AU - Van Der Laan, S.W.

AU - Bradfield, J.P.

AU - Wood, A.R.

AU - Bonnefond, A.

AU - Ahluwalia, T.S.

AU - Hall, L.M.

AU - Yazar, Seyhan

AU - Mackey, David

PY - 2015

Y1 - 2015

N2 - © 2015 Macmillan Publishers Limited. All rights reserved. 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.

AB - © 2015 Macmillan Publishers Limited. All rights reserved. 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.

U2 - 10.1038/nature14618

DO - 10.1038/nature14618

M3 - Article

C2 - 26131930

SN - 0028-0836

VL - 523

SP - 459

EP - 462

JO - Nature

JF - Nature

IS - 7561

ER -

Directional dominance on stature and cognition in diverse human populations

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this