King's College London

Research portal

Directional dominance on stature and cognition in diverse human populations

Research output: Contribution to journalArticlepeer-review

Standard

Directional dominance on stature and cognition in diverse human populations. / Joshi, Peter K; Esko, Tonu; Mattsson, Hannele et al.

In: NATURE, Vol. 523, No. 7561, 23.07.2015, p. 459-462.

Research output: Contribution to journalArticlepeer-review

Harvard

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, A-E, Kacprowski, T, Bjonnes, A, van der Spek, A, Wu, Y, Giri, AK, Yanek, LR, Wang, L, Hofer, E, Rietveld, CA, Lataniotis, L, Wood, AR, Hammond, CJ, Harris, SE, Hysi, PG, Lehne, B, Menni, C, Wilson, JG, Spector, TD, Weir, DR, Chambers, JC & BioBank Japan Project 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

APA

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., ... BioBank Japan Project (2015). Directional dominance on stature and cognition in diverse human populations. NATURE, 523(7561), 459-462. https://doi.org/10.1038/nature14618

Vancouver

Joshi PK, Esko T, Mattsson H, Eklund N, Gandin I, Nutile T et al. Directional dominance on stature and cognition in diverse human populations. NATURE. 2015 Jul 23;523(7561):459-462. https://doi.org/10.1038/nature14618

Author

Joshi, Peter K ; Esko, Tonu ; Mattsson, Hannele et al. / Directional dominance on stature and cognition in diverse human populations. In: NATURE. 2015 ; Vol. 523, No. 7561. pp. 459-462.

Bibtex Download

@article{7b8926faaaa6457e92343098577e4a6f,
title = "Directional dominance on stature and cognition in diverse human populations",
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, Body Height, Cholesterol, LDL, Cognition, Cohort Studies, Educational Status, Female, Forced Expiratory Volume, Genome, Human, Homozygote, Humans, Lung Volume Measurements, Male, Phenotype",
author = "Joshi, {Peter K} and Tonu Esko and Hannele Mattsson and Niina Eklund and Ilaria Gandin and Teresa Nutile and Jackson, {Anne U} and Claudia Schurmann and Smith, {Albert V} and Weihua Zhang and Yukinori Okada and Alena Stan{\v c}{\'a}kov{\'a} and Faul, {Jessica D} and Wei Zhao and Bartz, {Traci M} and Concas, {Maria Pina} and Nora Franceschini and Stefan Enroth and Veronique Vitart and Stella Trompet and Xiuqing Guo and Chasman, {Daniel I} and O'Connel, {Jeffrey R} and Tanguy Corre and Nongmaithem, {Suraj S} and Yuning Chen and Massimo Mangino and Daniela Ruggiero and Michela Traglia and Aliki-Eleni Farmaki and Tim Kacprowski and Andrew Bjonnes and {van der Spek}, Ashley and Ying Wu and Giri, {Anil K} and Yanek, {Lisa R} and Lihua Wang and Edith Hofer and Rietveld, {Cornelius A} and Lazaros Lataniotis and Wood, {Andrew R} and Hammond, {Christopher J} and Harris, {Sarah E} and Hysi, {Pirro G} and Benjamin Lehne and Cristina Menni and Wilson, {James G} and Spector, {Tim D} and Weir, {David R} and Chambers, {John C} and {BioBank Japan Project}",
year = "2015",
month = jul,
day = "23",
doi = "10.1038/nature14618",
language = "English",
volume = "523",
pages = "459--462",
journal = "NATURE",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7561",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

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

AU - Joshi, Peter K

AU - Esko, Tonu

AU - Mattsson, Hannele

AU - Eklund, Niina

AU - Gandin, Ilaria

AU - Nutile, Teresa

AU - Jackson, Anne U

AU - Schurmann, Claudia

AU - Smith, Albert V

AU - Zhang, Weihua

AU - Okada, Yukinori

AU - Stančáková, Alena

AU - Faul, Jessica D

AU - Zhao, Wei

AU - Bartz, Traci M

AU - Concas, Maria Pina

AU - Franceschini, Nora

AU - Enroth, Stefan

AU - Vitart, Veronique

AU - Trompet, Stella

AU - Guo, Xiuqing

AU - Chasman, Daniel I

AU - O'Connel, Jeffrey R

AU - Corre, Tanguy

AU - Nongmaithem, Suraj S

AU - Chen, Yuning

AU - Mangino, Massimo

AU - Ruggiero, Daniela

AU - Traglia, Michela

AU - Farmaki, Aliki-Eleni

AU - Kacprowski, Tim

AU - Bjonnes, Andrew

AU - van der Spek, Ashley

AU - Wu, Ying

AU - Giri, Anil K

AU - Yanek, Lisa R

AU - Wang, Lihua

AU - Hofer, Edith

AU - Rietveld, Cornelius A

AU - Lataniotis, Lazaros

AU - Wood, Andrew R

AU - Hammond, Christopher J

AU - Harris, Sarah E

AU - Hysi, Pirro G

AU - Lehne, Benjamin

AU - Menni, Cristina

AU - Wilson, James G

AU - Spector, Tim D

AU - Weir, David R

AU - Chambers, John C

AU - BioBank Japan Project

PY - 2015/7/23

Y1 - 2015/7/23

N2 - 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 - 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.

KW - Biological Evolution

KW - Blood Pressure

KW - Body Height

KW - Cholesterol, LDL

KW - Cognition

KW - Cohort Studies

KW - Educational Status

KW - Female

KW - Forced Expiratory Volume

KW - Genome, Human

KW - Homozygote

KW - Humans

KW - Lung Volume Measurements

KW - Male

KW - Phenotype

U2 - 10.1038/nature14618

DO - 10.1038/nature14618

M3 - Article

C2 - 26131930

VL - 523

SP - 459

EP - 462

JO - NATURE

JF - NATURE

SN - 0028-0836

IS - 7561

ER -

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454