NDLI: Directional dominance on stature and cognition in diverse human populations

Content Provider	PubMed Central
Author	Joshi, Peter K. Esko, Tonu Mattsson, Hannele Eklund, Niina Gandin, Ilaria Nutile, Teresa Jackson, Anne U. Schurmann, Claudia Smith, Albert V. Zhang, Weihua Okada, Yukinori Stančáková, Alena Faul, Jessica D. Zhao, Wei Bartz, Traci M. Concas, Maria Pina Franceschini, Nora Enroth, Stefan Vitart, Veronique Trompet, Stella Guo, Xiuqing Chasman, Daniel I. O’connel, Jeffery R. Corre, Tanguy Nongmaithem, Suraj S. Chen, Yuning Mangino, Massimo Ruggiero, Daniela Traglia, Michela Farmaki, Aliki-eleni Kacprowski, Tim Andrew, Bjonnes Spek, Ashley Van Der Wu, Ying Giri, Anil K. Yanek, Lisa R. Wang, Lihua Hofer, Edith Rietveld, Cornelius A. Mcleod, Olga Cornelis, Marilyn C. Pattaro, Cristian Verweij, Niek Baumbach, Clemens Abdellaoui, Abdel Warren, Helen R. Vuckovic, Dragana Mei, Hao Bouchard, Claude Perry, John R. B. Cappellani, Stefania Mirza, Saira S. Benton, Miles C. Broeckel, Ulrich Medland, Sarah E. Lind, Penelope A. Malerba, Giovanni Drong, Alexander Yengo, Loic Bielak, Lawrence F. Zhi, Degui Most, Peter J. Van Der Shriner, Daniel Mägi, Reedik Hemani, Gibran Karaderi, Tugce Wang, Zhaoming Liu, Tian Demuth, Ilja Zhao, Jing Hua Meng, Weihua Lataniotis, Lazaros Laan, Sander W. Van Der Bradfield, Jonathan P. Wood, Andrew R. Bonnefond, Amelie Ahluwalia, Tarunveer S. Hall, Leanne M. Salvi, Erika Yazar, Seyhan Carstensen, Lisbeth Haan, Hugoline G. De Abney, Mark Afzal, Uzma Allison, Matthew A. Amin, Najaf Asselbergs, Folkert W. Bakker, Stephan J. L. Barr, R. Graham Baumeister, Sebastian E. Benjamin, Daniel J. Bergmann, Sven Boerwinkle, Eric Bottinger, Erwin P. Campbell, Archie Chakravarti, Aravinda Chan, Yingleong Chanock, Stephen J. Chen, Constance Chen, Y. D. Ida Collins, Francis S. Connell, John Correa, Adolfo Cupples, L. Adrienne Smith, George Davey Davies, Gail Dörr, Marcus Ehret, Georg Ellis, Stephen B. Feenstra, Bjarke Feitosa, Mary F. Ford, Ian Fox, Caroline S. Frayling, Timothy M. Friedrich, Nele Geller, Frank Scotland, Generation Irina, Gillham-nasenya Gottesman, Omri Graff, Misa Grodstein, Francine Gu, Charles Haley, Chris Hammond, Christopher J. Harris, Sarah E. Harris, Tamara B. Hastie, Nicholas D. Heard-costa, Nancy L. Heikkilä, Kauko Hocking, Lynne J. Homuth, Georg Hottenga, Jouke-jan Huang, Jinyan Huffman, Jennifer E. Hysi, Pirro G. Ikram, M. Arfan Ingelsson, Erik Joensuu, Anni Johansson, Åsa Jousilahti, Pekka Wouter, Jukema J. Mika, Kähönen Kamatani, Yoichiro Kanoni, Stavroula Kerr, Shona M. Khan, Nazir M. Philipp, Koellinger Koistinen, Heikki A. Kooner, Manraj K. Kubo, Michiaki Kuusisto, Johanna Lahti, Jari Launer, Lenore J. Lea, Rodney A. Lehne, Benjamin Lehtimäki, Terho Liewald, David C. M. Lind, Lars Loh, Marie Lokki, Marja-liisa London, Stephanie J. Loomis, Stephanie J. Loukola, Anu Lu, Yingchang Lumley, Thomas Lundqvist, Annamari Männistö, Satu Pedro, Marques-vidal Corrado, Masciullo Angela, Matchan Mathias, Rasika A. Matsuda, Koichi Meigs, James B. Meisinger, Christa Meitinger, Thomas Cristina, Menni Mentch, Frank D. Mihailov, Evelin Milani, Lili Montasser, May E. Montgomery, Grant W. Morrison, Alanna Myers, Richard H. Nadukuru, Rajiv Navarro, Pau Nelis, Mari Nieminen, Markku S. Nolte, Ilja M. O’connor, George T. Ogunniyi, Adesola Padmanabhan, Sandosh Palmas, Walter R. Pankow, James S. Inga, Patarcic Pavani, Francesca Peyser, Patricia A. Pietilainen, Kirsi Poulter, Neil Prokopenko, Inga Ralhan, Sarju Redmond, Paul Rich, Stephen S. Rissanen, Harri Robino, Antonietta Rose, Lynda M. Rose, Richard Sala, Cinzia Babatunde, Salako Salomaa, Veikko Sarin, Antti-pekka Saxena, Richa Schmidt, Helena Scott, Laura J. Scott, William R. Sennblad, Bengt Seshadri, Sudha Sever, Peter Shrestha, Smeeta Smith, Blair H. Smith, Jennifer A. Soranzo, Nicole Nona, Sotoodehnia Southam, Lorraine Stanton, Alice V. Stathopoulou, Maria G. Strauch, Konstantin Strawbridge, Rona J. Suderman, Matthew J. Tandon, Nikhil Tang, Sian-tsun Taylor, Kent D. Tayo, Bamidele O. Maria, Töglhofer Anna Tomaszewski, Maciej Natalia, Tšernikova Tuomilehto, Jaakko Uitterlinden, Andre G. Vaidya, Dhananjay Van, Hylckama Vlieg Astrid Setten, Jessica Van Vasankari, Tuula Vedantam, Sailaja Vlachopoulou, Efthymia Diego, Vozzi Vuoksimaa, Eero Waldenberger, Melanie Ware, Erin B. Wentworth-shields, William Whitfield, John B. Wild, Sarah Willemsen, Gonneke Yajnik, Chittaranjan S. Yao, Jie Zaza, Gianluigi Zhu, Xiaofeng Salem, Rany M. Melbye, Mads Bisgaard, Hans Samani, Nilesh J. Cusi, Daniele Mackey, David A. Cooper, Richard S. Philippe, Froguel Gerard, Pasterkamp Grant, Struan F. A. Hakonarson, Hakon Ferrucci, Luigi Scott, Robert A. Morris, Andrew D. Palmer, Colin N. A. George, Dedoussis Panos, Deloukas Bertram, Lars Lindenberger, Ulman Berndt, Sonja I. Lindgren, Cecilia M. Timpson, Nicholas J. Anke, Tönjes Munroe, Patricia B. Sørensen, Thorkild I. A. Rotimi, Charles N. Arnett, Donna K. Oldehinkel, Albertine J. Kardia, Sharon L. R. Beverley, Balkau Gambaro, Giovanni Morris, Andrew P. Eriksson, Johan G. Wright, Margie J. Martin, Nicholas G. Hunt, Steven C. Starr, John M. Deary, Ian J. Griffiths, Lyn R. Henning, Tiemeier Nicola, Pirastu Kaprio, Jaakko Wareham, Nicholas J. Louis, Pérusse Wilson, James G. Girotto, Giorgia Caulfield, Mark J. Olli, Raitakari Boomsma, Dorret I. Gieger, Christian Harst, Pim Van Der Hicks, Andrew A. Kraft, Peter Sinisalo, Juha Paul, Knekt Johannesson, Magnus Magnusson, Patrik K. E. Anders, Hamsten Schmidt, Reinhold Borecki, Ingrid B. Vartiainen, Erkki Becker, Diane M. Bharadwaj, Dwaipayan Mohlke, Karen L. Boehnke, Michael Duijn, Cornelia M. Van Sanghera, Dharambir K. Teumer, Alexander Zeggini, Eleftheria Andres, Metspalu Gasparini, Paolo Ulivi, Sheila Ober, Carole Toniolo, Daniela Rudan, Igor Porteous, David J. Ciullo, Marina Spector, Tim D. Hayward, Caroline Dupuis, Josée Loos, Ruth J. F. Wright, Alan F. Chandak, Giriraj R. Vollenweider, Peter Shuldiner, Alan Ridker, Paul M. Rotter, Jerome I. Sattar, Naveed Gyllensten, Ulf North, Kari E. Mario, Pirastu Psaty, Bruce M. Weir, David R. Laakso, Markku Gudnason, Vilmundur Takahashi, Atsushi Chambers, John C. Kooner, Jaspal S. Strachan, David P. Campbell, Harry Hirschhorn, Joel N. Perola, Markus Polašek, Ozren Wilson, James F. Project, The BioBank Japan
Abstract	Homozygosity has long been associated with rare, often devastating, Mendelian disorders 1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness 2 . However, the effect of the more distant parental relatedness 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, ROH), 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 ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). 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 convincing evidence for the first time 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 (LDL) 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.
Related Links	http://dx.doi.org/10.1038/nature14618
Ending Page	462
Page Count	4
Starting Page	459
File Format	PDF
ISSN	00280836
e-ISSN	14764687
Journal	Nature
Issue Number	7561
Volume Number	523
Language	English
Publisher Date	2015-07-01
Access Restriction	Open
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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