Directional dominance on stature and cognition in diverse human populations.

Authors:
Dr. Dharambir K Sanghera
Dr. Dharambir K Sanghera
University of Oklahoma Health Sciences Center
Professor
Oklahoma City, Oklahoma | United States
Mr Anil K Giri, M Sc
Mr Anil K Giri, M Sc
CSIR-Institute of genomics and Integrative Biology
Data Analytics
New Delhi, 110025 | India
Dr Miles Benton, PhD
Dr Miles Benton, PhD
Queensland University of Technology
Post-Doctoral Research Fellow
Bioinformatics; Computational Genetics
Brisbane, QLD | Australia
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 Stančáková Jessica D Faul Wei Zhao Traci M Bartz Maria Pina Concas Nora Franceschini Stefan Enroth Veronique Vitart Stella Trompet Xiuqing Guo Daniel I Chasman Jeffery 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 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 Penelope A Lind Giovanni Malerba Alexander Drong Loic Yengo Lawrence F Bielak Degui Zhi Peter J van der Most Daniel Shriner Reedik Mägi 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 Leanne M 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 Francis S Collins John Connell Adolfo Correa L Adrienne Cupples George Davey Smith Gail Davies Marcus Dörr Georg Ehret Stephen B Ellis Bjarke Feenstra Mary F Feitosa Ian Ford Caroline S Fox Timothy M Frayling Nele Friedrich Frank Geller Generation Scotland Irina Gillham-Nasenya Omri Gottesman Misa Graff Francine Grodstein Charles Gu Chris Haley Christopher J Hammond Sarah E Harris Tamara B Harris Nicholas D Hastie Nancy L Heard-Costa Kauko Heikkilä Lynne J Hocking Georg Homuth Jouke-Jan Hottenga Jinyan Huang Jennifer E Huffman Pirro G Hysi M Arfan Ikram Erik Ingelsson Anni Joensuu Åsa Johansson Pekka Jousilahti J Wouter Jukema Mika Kähönen Yoichiro Kamatani Stavroula Kanoni Shona M Kerr Nazir M Khan Philipp Koellinger Heikki A Koistinen Manraj K Kooner Michiaki Kubo Johanna Kuusisto Jari Lahti Lenore J Launer Rodney A Lea Benjamin Lehne Terho Lehtimäki David C M Liewald Lars Lind Marie Loh Marja-Liisa Lokki Stephanie J London Stephanie J Loomis Anu Loukola Yingchang Lu Thomas Lumley Annamari Lundqvist Satu Männistö Pedro Marques-Vidal Corrado Masciullo Angela Matchan Rasika A Mathias Koichi Matsuda James B Meigs Christa Meisinger Thomas Meitinger Cristina Menni Frank D Mentch Evelin Mihailov Lili Milani May E Montasser Grant W Montgomery Alanna Morrison Richard H Myers Rajiv Nadukuru Pau Navarro Mari Nelis Markku S Nieminen Ilja M Nolte George T O'Connor Adesola Ogunniyi Sandosh Padmanabhan Walter R Palmas James S Pankow Inga Patarcic Francesca 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M Becker Dwaipayan Bharadwaj Karen L Mohlke Michael Boehnke Cornelia M van Duijn Alexander Teumer Eleftheria Zeggini Andres Metspalu Paolo Gasparini Sheila Ulivi Carole Ober Daniela Toniolo Igor Rudan David J Porteous Marina Ciullo Tim D Spector Caroline Hayward Josée Dupuis Ruth J F Loos Alan F Wright Giriraj R Chandak Peter Vollenweider Alan Shuldiner Paul M Ridker Jerome I Rotter Naveed Sattar Ulf Gyllensten Kari E North Mario Pirastu Bruce M Psaty David R Weir Markku Laakso Vilmundur Gudnason Atsushi Takahashi John C Chambers Jaspal S Kooner David P Strachan Harry Campbell Joel N Hirschhorn Markus Perola Ozren Polašek James F Wilson

Nature 2015 Jul 1;523(7561):459-462. Epub 2015 Jul 1.

Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.

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.

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http://dx.doi.org/10.1038/nature14618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516141PMC
July 2015
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References

(Supplied by CrossRef)
Article in Lancet
A Garrod et al.
Lancet 1902

C Darwin et al.
1868
Article in Am. J. Hum. Genet.
R McQuillan et al.
Am. J. Hum. Genet. 2008
Article in PLoS Genet.
R McQuillan et al.
PLoS Genet. 2012
Article in Genetics
I Rudan et al.
Genetics 2003
Article in Hum. Mol. Genet.
H Campbell et al.
Hum. Mol. Genet. 2007
Article in Nature Rev. Genet.
D Charlesworth et al.
Nature Rev. Genet. 2009

S Wright et al.
1977
Article in Am. Nat.
S Wright et al.
Am. Nat. 1922
Article in Am. J. Hum. Genet.
KW Broman et al.
Am. J. Hum. Genet. 1999
Article in Hum. Mol. Genet.
J Gibson et al.
Hum. Mol. Genet. 2006

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