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

Macé, Aurélien, Tuke, Marcus A., Deelen, Patrick, Kristiansson, Kati, Mattsson, Hannele, Nõukas, Margit, Sapkota, Yadav, Schick, Ursula, Porcu, Eleonora, Rüeger, Sina, McDaid, Aaron F., Porteous, David, Winkler, Thomas W., Salvi, Erika, Shrine, Nick, Liu, Xueping, Ang, Wei Q., Zhang, Weihua, Feitosa, Mary F., Venturini, Cristina, Van Der Most, Peter J., Rosengren, Anders, Wood, Andrew R., Beaumont, Robin N., Jones, Samuel E., Ruth, Katherine S., Yaghootkar, Hanieh, Tyrrell, Jessica, Havulinna, Aki S., Boers, Harmen, Mägi, Reedik, Kriebel, Jennifer, Müller-Nurasyid, Martina, Perola, Markus, Nieminen, Markku, Lokki, Marja-Liisa, Kähönen, Mika, Viikari, Jorma S., Geller, Frank, Lahti, Jari, Palotie, Aarno, Koponen, Päivikki, Lundqvist, Annamari, Rissanen, Harri, Bottinger, Erwin P., Afaq, Saima, Wojczynski, Mary K., Lenzini, Petra, Nolte, Ilja M., Sparsø, Thomas, Schupf, Nicole, Christensen, Kaare, Perls, Thomas T., Newman, Anne B., Werge, Thomas, Snieder, Harold, Spector, Timothy D., Chambers, John C., Koskinen, Seppo, Melbye, Mads, Raitakari, Olli T., Lehtimäki, Terho, Tobin, Martin D., Wain, Louise V., Sinisalo, Juha, Peters, Annette, Meitinger, Thomas, Martin, Nicholas G., Wray, Naomi R., Montgomery, Grant W., Medland, Sarah E., Swertz, Morris A., Vartiainen, Erkki, Borodulin, Katja, Männistö, Satu, Murray, Anna, Bochud, Murielle, Jacquemont, Sébastien, Rivadeneira, Fernando, Hansen, Thomas F., Oldehinkel, Albertine J., Mangino, Massimo, Province, Michael A., Deloukas, Panos, Kooner, Jaspal S., Freathy, Rachel M., Pennell, Craig, Feenstra, Bjarke, Strachan, David P., Lettre, Guillaume, Hirschhorn, Joel, Cusi, Daniele, Heid, Iris M., Hayward, Caroline, Männik, Katrin, Beckmann, Jacques S., Loos, Ruth J. F., Nyholt, Dale R., Metspalu, Andres, Eriksson, Johan G., Weedon, Michael N., Salomaa, Veikko, Franke, Lude, Reymond, Alexandre, Frayling, Timothy M. and Kutalik, Zoltán (2017) CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits. Nature Communications, 8 1: 744. doi:10.1038/s41467-017-00556-x


Author Macé, Aurélien
Tuke, Marcus A.
Deelen, Patrick
Kristiansson, Kati
Mattsson, Hannele
Nõukas, Margit
Sapkota, Yadav
Schick, Ursula
Porcu, Eleonora
Rüeger, Sina
McDaid, Aaron F.
Porteous, David
Winkler, Thomas W.
Salvi, Erika
Shrine, Nick
Liu, Xueping
Ang, Wei Q.
Zhang, Weihua
Feitosa, Mary F.
Venturini, Cristina
Van Der Most, Peter J.
Rosengren, Anders
Wood, Andrew R.
Beaumont, Robin N.
Jones, Samuel E.
Ruth, Katherine S.
Yaghootkar, Hanieh
Tyrrell, Jessica
Havulinna, Aki S.
Boers, Harmen
Mägi, Reedik
Kriebel, Jennifer
Müller-Nurasyid, Martina
Perola, Markus
Nieminen, Markku
Lokki, Marja-Liisa
Kähönen, Mika
Viikari, Jorma S.
Geller, Frank
Lahti, Jari
Palotie, Aarno
Koponen, Päivikki
Lundqvist, Annamari
Rissanen, Harri
Bottinger, Erwin P.
Afaq, Saima
Wojczynski, Mary K.
Lenzini, Petra
Nolte, Ilja M.
Sparsø, Thomas
Schupf, Nicole
Christensen, Kaare
Perls, Thomas T.
Newman, Anne B.
Werge, Thomas
Snieder, Harold
Spector, Timothy D.
Chambers, John C.
Koskinen, Seppo
Melbye, Mads
Raitakari, Olli T.
Lehtimäki, Terho
Tobin, Martin D.
Wain, Louise V.
Sinisalo, Juha
Peters, Annette
Meitinger, Thomas
Martin, Nicholas G.
Wray, Naomi R.
Montgomery, Grant W.
Medland, Sarah E.
Swertz, Morris A.
Vartiainen, Erkki
Borodulin, Katja
Männistö, Satu
Murray, Anna
Bochud, Murielle
Jacquemont, Sébastien
Rivadeneira, Fernando
Hansen, Thomas F.
Oldehinkel, Albertine J.
Mangino, Massimo
Province, Michael A.
Deloukas, Panos
Kooner, Jaspal S.
Freathy, Rachel M.
Pennell, Craig
Feenstra, Bjarke
Strachan, David P.
Lettre, Guillaume
Hirschhorn, Joel
Cusi, Daniele
Heid, Iris M.
Hayward, Caroline
Männik, Katrin
Beckmann, Jacques S.
Loos, Ruth J. F.
Nyholt, Dale R.
Metspalu, Andres
Eriksson, Johan G.
Weedon, Michael N.
Salomaa, Veikko
Franke, Lude
Reymond, Alexandre
Frayling, Timothy M.
Kutalik, Zoltán
Title CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2017-09-29
Year available 2017
Sub-type Article (original research)
DOI 10.1038/s41467-017-00556-x
Open Access Status DOI
Volume 8
Issue 1
Start page 744
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract 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/m2). 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/m2 for each Mb of total deletion burden (P = 2.5 × 10-10, 6.0 × 10-5, and 2.9 × 10-3). 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.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 323195
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 03 Nov 2017, 16:22:34 EST