CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits.

Authors:
Saima Afaq
Saima Afaq
Institute of Public health and Social Sciences, Khyber medical university Peshawar Pakistan
Dr
Peshawar, KPK | Pakistan
Aurélien Macé Marcus A Tuke Patrick Deelen Kati Kristiansson Hannele Mattsson Margit Nõukas Yadav Sapkota Ursula Schick Eleonora Porcu Sina Rüeger Aaron F McDaid David Porteous Thomas W Winkler Erika Salvi Nick Shrine Xueping Liu Wei Q Ang Weihua Zhang Mary F Feitosa Cristina Venturini Peter J van der Most Anders Rosengren Andrew R Wood Robin N Beaumont Samuel E Jones Katherine S Ruth Hanieh Yaghootkar Jessica Tyrrell Aki S Havulinna Harmen Boers Reedik Mägi Jennifer Kriebel Martina Müller-Nurasyid Markus Perola Markku Nieminen Marja-Liisa Lokki Mika Kähönen Jorma S Viikari Frank Geller Jari Lahti Aarno Palotie Päivikki Koponen Annamari Lundqvist Harri Rissanen Erwin P Bottinger Mary K Wojczynski Petra Lenzini Ilja M Nolte Thomas Sparsø Nicole Schupf Kaare Christensen Thomas T Perls Anne B Newman Thomas Werge Harold Snieder Timothy D Spector John C Chambers Seppo Koskinen Mads Melbye Olli T Raitakari Terho Lehtimäki Martin D Tobin Louise V Wain Juha Sinisalo Annette Peters Thomas Meitinger Nicholas G Martin Naomi R Wray Grant W Montgomery Sarah E Medland Morris A Swertz Erkki Vartiainen Katja Borodulin Satu Männistö Anna Murray Murielle Bochud Sébastien Jacquemont Fernando Rivadeneira Thomas F Hansen Albertine J Oldehinkel Massimo Mangino Michael A Province Panos Deloukas Jaspal S Kooner Rachel M Freathy Craig Pennell Bjarke Feenstra David P Strachan Guillaume Lettre Joel Hirschhorn Daniele Cusi Iris M Heid Caroline Hayward Katrin Männik Jacques S Beckmann Ruth J F Loos Dale R Nyholt Andres Metspalu Johan G Eriksson Michael N Weedon Veikko Salomaa Lude Franke Alexandre Reymond Timothy M Frayling Zoltán Kutalik

Nat Commun 2017 09 29;8(1):744. Epub 2017 Sep 29.

Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, 1010, Switzerland.

There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m for each Mb of total deletion burden (P = 2.5 × 10, 6.0 × 10, and 2.9 × 10). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.

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http://dx.doi.org/10.1038/s41467-017-00556-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622064PMC
September 2017
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References

(Supplied by CrossRef)

HH Maes et al.
Behav. Genet. 1997

PM Visscher et al.
Am. J. Hum. Genet. 2012

N Zaitlen et al.
PLoS Genet. 2013

J Hjelmborg et al.
Obesity 2008

AJ Stunkard et al.
N. Engl. J. Med. 1990

PM Visscher et al.
PLoS Genet. 2006

K Silventoinen et al.
Twin Res. 2003

AE Locke et al.
Nature 2015

AR Wood et al.
Nat. Genet. 2014

E Marouli et al.
Nature 2017

J Yang et al.
Nat. Genet. 2015

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