Directional dominance on stature and cognition in diverse human populations

Peter K. Joshi; Tonu Esko; Hannele Mattsson; Niina Eklund; Ilaria Gandin; Teresa Nutile; Anne U. Jackson; Claudia Schurmann; Albert V. Smith; Weihua Zhang; Yukinori Okada; Alena Stancakova; Jessica D. Faul; Wei Zhao; Traci M. Bartz; Maria Pina Concas; Nora Franceschini; Stefan Enroth; Veronique Vitart; Stella Trompet; Xiuqing Guo; Daniel I. Chasman; Jeffrey R. O'Connel; Tanguy Corre; Suraj S. Nongmaithem; Yuning Chen; Massimo Mangino; Daniela Ruggiero; Michela Traglia; Aliki-Eleni Farmaki; Tim Kacprowski; Andrew Bjonnes; Ashley van der Spek; Ying Wu; Anil K. Giri; Lisa R. Yanek; Lihua Wang; Edith Hofer; Cornelius A. Rietveld; Olga McLeod; Marilyn C. Cornelis; Cristian Pattaro; Niek Verweij; Clemens Baumbach; Abdel Abdellaoui; Helen R. Warren; Dragana Vuckovic; Hao Mei; Claude Bouchard; John R. B. Perry; Stefania Cappellani; Saira S. Mirza; Miles C. Benton; Ulrich Broeckel; Sarah E. Medland; PenelopeA Lind; Giovanni Malerba; Alexander Drong; Loic Yengo; Lawrence F. Bielak; Degui Zhi; Peter J. van der Most; Daniel Shriner; Reedik Maegi; Gibran Hemani; Tugce Karaderi; Zhaoming Wang; Tian Liu; Ilja Demuth; Jing Hua Zhao; Weihua Meng; Lazaros Lataniotis; Sander W. van der Laan; Jonathan P. Bradfield; Andrew R. Wood; Amelie Bonnefond; Tarunveer S. Ahluwalia; LeanneM Hall; Erika Salvi; Seyhan Yazar; Lisbeth Carstensen; Hugoline G. de Haan; Mark Abney; Uzma Afzal; Matthew A. Allison; Najaf Amin; Folkert W. Asselbergs; Stephan J. L. Bakker; R. Graham Barr; Sebastian E. Baumeister; Daniel J. Benjamin; Sven Bergmann; Eric Boerwinkle; Erwin P. Bottinger; Archie Campbell; Aravinda Chakravarti; Yingleong Chan; Stephen J. Chanock; Constance Chen; Y. -D. Ida Chen; BioBank Japan Project; Inga Prokopenko

doi:10.1038/nature14618

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Directional dominance on stature and cognition in diverse human populations

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Directional dominance on stature and cognition in diverse human populations

Peter K. Joshi, Tonu Esko, Hannele Mattsson, Niina Eklund, Ilaria Gandin, Teresa Nutile, Anne U. Jackson, Claudia Schurmann, Albert V. Smith, Weihua Zhang, …

Nature (London), Vol.523(7561), pp.459-U176

23/07/2015

DOI: https://doi.org/10.1038/nature14618

PMID: 26131930

Abstract

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Homozygosity has long been associated with rare, often devastating, Mendelian disorders(1), and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness(2). 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(3,4). 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 x 10(-300), 2.1 x 10(-6), 2.5 x 10(-10) and 1.8 x 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(5,6), 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(7), 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.

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Title: Directional dominance on stature and cognition in diverse human populations
Creators: Peter K. Joshi - University of Edinburgh
Tonu Esko - Boston Children's Hospital
Hannele Mattsson - University of Tartu
Niina Eklund - Finnish Institute for Health and Welfare
Ilaria Gandin - Finnish Institute for Health and Welfare
Teresa Nutile - University of Trieste
Anne U. Jackson - Institute of Genetics and Biophysics
Claudia Schurmann - University of Michigan–Ann Arbor
Albert V. Smith - Icahn School of Medicine at Mount Sinai
Weihua Zhang - University of London
Yukinori Okada - Imperial College London
Alena Stancakova - Tokyo Medical and Dental University
Jessica D. Faul - University of Eastern Finland
Wei Zhao - University of Michigan–Ann Arbor
Traci M. Bartz - University of Michigan–Ann Arbor
Maria Pina Concas - University of Washington
Nora Franceschini - National Research Council
Stefan Enroth - University of North Carolina at Chapel Hill
Veronique Vitart - Uppsala University
Stella Trompet - University of Edinburgh
Xiuqing Guo - Leiden University Medical Center
Daniel I. Chasman - The Lundquist Institute
Jeffrey R. O'Connel - Supreme Council Of Health
Tanguy Corre - University of Maryland, Baltimore
Suraj S. Nongmaithem - University of Lausanne
Yuning Chen - Centre for Cellular and Molecular Biology
Massimo Mangino - Boston University
Daniela Ruggiero - King's College London
Michela Traglia - Institute of Genetics and Biophysics
Aliki-Eleni Farmaki - Harokopio University of Athens
Tim Kacprowski - Harokopio University of Athens
Andrew Bjonnes - Universitätsmedizin Greifswald
Ashley van der Spek - Massachusetts General Hospital
Ying Wu - Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA
Anil K. Giri - University of North Carolina at Chapel Hill
Lisa R. Yanek - Institute of Genomics and Integrative Biology
Lihua Wang - Johns Hopkins University
Edith Hofer - Washington University in St. Louis
Cornelius A. Rietveld - Medical University of Graz
Olga McLeod - Erasmus University Rotterdam
Marilyn C. Cornelis - Karolinska Institutet
Cristian Pattaro - Brigham and Women's Hospital
Niek Verweij - Eurac Research
Clemens Baumbach - University Medical Center Groningen
Abdel Abdellaoui - Helmholtz Zentrum München
Helen R. Warren - Vrije Universiteit Amsterdam
Dragana Vuckovic - William Harvey Research Institute
Hao Mei - University of Trieste
Claude Bouchard - University of Mississippi Medical Center
John R. B. Perry - Pennington Biomedical Research Center
Stefania Cappellani - University of Cambridge
Saira S. Mirza - IRCCS Materno Infantile Burlo Garofolo
Miles C. Benton - Erasmus MC
Ulrich Broeckel - Queensland University of Technology
Sarah E. Medland - Medical College of Wisconsin
PenelopeA Lind - College Station Medical Center
Giovanni Malerba - QIMR Berghofer Medical Research Institute
Alexander Drong - University of Verona
Loic Yengo - University of Oxford
Lawrence F. Bielak - Centre National de la Recherche Scientifique
Degui Zhi - University of Michigan–Ann Arbor
Peter J. van der Most - University of Alabama at Birmingham
Daniel Shriner - University of Groningen
Reedik Maegi - University of Tartu
Gibran Hemani - University of Tartu
Tugce Karaderi - University of Bristol
Zhaoming Wang - NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA
Tian Liu - National Institutes of Health
Ilja Demuth - Max Planck Institute for Human Development
Jing Hua Zhao - Charité - Universitätsmedizin Berlin
Weihua Meng - MRC Epidemiology Unit
Lazaros Lataniotis - Ninewells Hospital
Sander W. van der Laan - Queen Mary University of London
Jonathan P. Bradfield - Heidelberg University
Andrew R. Wood - Children's Hospital of Philadelphia
Amelie Bonnefond - Royal Devon and Exeter Hospital
Tarunveer S. Ahluwalia - European Genomic Institute for Diabetes
LeanneM Hall - University of Leicester
Erika Salvi - University of Leicester
Seyhan Yazar - University of Milan
Lisbeth Carstensen - Lions Eye Institute
Hugoline G. de Haan - Statens Serum Institut
Mark Abney - Leiden University Medical Center
Uzma Afzal - University of Chicago
Matthew A. Allison - Ealing Hospital NHS Trust
Najaf Amin - University of California, San Diego
Folkert W. Asselbergs - Erasmus MC
Stephan J. L. Bakker - University Medical Center Utrecht
R. Graham Barr - University Medical Center Groningen
Sebastian E. Baumeister - Columbia University
Daniel J. Benjamin - Universitätsmedizin Greifswald
Sven Bergmann - Cornell University
Eric Boerwinkle - University of Lausanne
Erwin P. Bottinger - The University of Texas Health Science Center at Houston
Archie Campbell - Icahn School of Medicine at Mount Sinai
Aravinda Chakravarti - Western General Hospital
Yingleong Chan - Johns Hopkins University
Stephen J. Chanock - Lemuel Shattuck Hospital
Constance Chen - National Institutes of Health
Y. -D. Ida Chen - Harvard University
BioBank Japan Project
Inga Prokopenko - School of Biosciences
Publication Details: Nature (London), Vol.523(7561), pp.459-U176
Publisher: NATURE PORTFOLIO
Number of pages: 17
Date published: 23/07/2015
Grant note: MRC Human Genetics Unit "QTL in Health and Disease" programme; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) NNF10OC1013354 / Novo Nordisk Fonden; Novo Nordisk Foundation MR/K002414/1; MC_UU_12015/2; MC_PC_U127592696; G0701863; MR/N01104X/1; MC_U127561128; G0601966; MC_U106179472; G9521010; G1001799; G0700704; MC_UU_12013/3; MC_UU_12013/1; MC_UU_12015/1; G0700931; MC_PC_U127561128 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 1201677; G0701863; G0601966; MC_PC_13046; MR/K002414/1; MR/N01104X/1; G9815508; MC_PC_U127561128; MR/K006584/1; MC_UU_12015/2; MC_UU_12015/1; G0700931; G0700704; MC_UU_12013/1; MC_UU_12013/3; MC_PC_15018; MC_PC_U127592696; MC_PC_13048; MC_U106179471; G1001799; G9521010; MR/K026992/1; MC_U127561128; MC_U106179472 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) BB/F019394/1 / Biotechnology and Biological Sciences Research Council; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) CZB/4/505; ETM/55; CZB/4/710; CZD/16/6/4; CZD/16/6/2 / Chief Scientist Office BB/F019394/1 / BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) 15H05911; 15H05670; 25293168 / Grants-in-Aid for Scientific Research; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Japan Society for the Promotion of Science; Grants-in-Aid for Scientific Research (KAKENHI) UK Medical Research Council (MRC); UK Research & Innovation (UKRI); Medical Research Council UK (MRC) NF-SI-0514-10027; NF-SI-0512-10113; NF-SI-0512-10135; NF-SI-0513-10059; SRF/01/010 / National Institute for Health Research; National Institute for Health Research (NIHR)
Identifiers: 99928781002346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Directional dominance on stature and cognition in diverse human populations

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