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.
Original language | English |
---|---|
Article number | 744 |
Journal | Nature communications |
Volume | 8 |
Issue number | 1 |
DOIs | |
State | Published - Dec 1 2017 |
Fingerprint
Dive into the research topics of 'CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
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.; Kutalik, Zoltán.
In: Nature communications, Vol. 8, No. 1, 744, 01.12.2017.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits
AU - Macé, Aurélien
AU - Tuke, Marcus A.
AU - Deelen, Patrick
AU - Kristiansson, Kati
AU - Mattsson, Hannele
AU - Nõukas, Margit
AU - Sapkota, Yadav
AU - Schick, Ursula
AU - Porcu, Eleonora
AU - Rüeger, Sina
AU - McDaid, Aaron F.
AU - Porteous, David
AU - Winkler, Thomas W.
AU - Salvi, Erika
AU - Shrine, Nick
AU - Liu, Xueping
AU - Ang, Wei Q.
AU - Zhang, Weihua
AU - Feitosa, Mary F.
AU - Venturini, Cristina
AU - Van Der Most, Peter J.
AU - Rosengren, Anders
AU - Wood, Andrew R.
AU - Beaumont, Robin N.
AU - Jones, Samuel E.
AU - Ruth, Katherine S.
AU - Yaghootkar, Hanieh
AU - Tyrrell, Jessica
AU - Havulinna, Aki S.
AU - Boers, Harmen
AU - Mägi, Reedik
AU - Kriebel, Jennifer
AU - Müller-Nurasyid, Martina
AU - Perola, Markus
AU - Nieminen, Markku
AU - Lokki, Marja Liisa
AU - Kähönen, Mika
AU - Viikari, Jorma S.
AU - Geller, Frank
AU - Lahti, Jari
AU - Palotie, Aarno
AU - Koponen, Päivikki
AU - Lundqvist, Annamari
AU - Rissanen, Harri
AU - Bottinger, Erwin P.
AU - Afaq, Saima
AU - Wojczynski, Mary K.
AU - Lenzini, Petra
AU - Nolte, Ilja M.
AU - Sparsø, Thomas
AU - Schupf, Nicole
AU - Christensen, Kaare
AU - Perls, Thomas T.
AU - Newman, Anne B.
AU - Werge, Thomas
AU - Snieder, Harold
AU - Spector, Timothy D.
AU - Chambers, John C.
AU - Koskinen, Seppo
AU - Melbye, Mads
AU - Raitakari, Olli T.
AU - Lehtimäki, Terho
AU - Tobin, Martin D.
AU - Wain, Louise V.
AU - Sinisalo, Juha
AU - Peters, Annette
AU - Meitinger, Thomas
AU - Martin, Nicholas G.
AU - Wray, Naomi R.
AU - Montgomery, Grant W.
AU - Medland, Sarah E.
AU - Swertz, Morris A.
AU - Vartiainen, Erkki
AU - Borodulin, Katja
AU - Männistö, Satu
AU - Murray, Anna
AU - Bochud, Murielle
AU - Jacquemont, Sébastien
AU - Rivadeneira, Fernando
AU - Hansen, Thomas F.
AU - Oldehinkel, Albertine J.
AU - Mangino, Massimo
AU - Province, Michael A.
AU - Deloukas, Panos
AU - Kooner, Jaspal S.
AU - Freathy, Rachel M.
AU - Pennell, Craig
AU - Feenstra, Bjarke
AU - Strachan, David P.
AU - Lettre, Guillaume
AU - Hirschhorn, Joel
AU - Cusi, Daniele
AU - Heid, Iris M.
AU - Hayward, Caroline
AU - Männik, Katrin
AU - Beckmann, Jacques S.
AU - Loos, Ruth J.F.
AU - Nyholt, Dale R.
AU - Metspalu, Andres
AU - Eriksson, Johan G.
AU - Weedon, Michael N.
AU - Salomaa, Veikko
AU - Franke, Lude
AU - Reymond, Alexandre
AU - Frayling, Timothy M.
AU - Kutalik, Zoltán
N1 - Funding Information: This research has been conducted using the UK Biobank Resource. This research has been conducted using the Danish National Biobank resource. The authors are grateful to the Raine Study participants and their families, and to the Raine Study research staff for cohort co-ordination and data collection. QIMR is grateful to the twins and their families for their generous participation in these studies. We would like to thank staff at the Queensland Institute of Medical Research: Anjali Henders, Dixie Statham, Lisa Bowdler, Ann Eldridge, and Marlene Grace for sample collection, processing and genotyping, Scott Gordon, Brian McEvoy, Belinda Cornes and Beben Benyamin for data QC and preparation, and David Smyth and Harry Beeby for IT support. HBCS Acknowledgements: We thank all study participants as well as everybody involved in the Helsinki Birth Cohort Study. Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland, the Finnish Diabetes Research Society, Folkhälsan Research Foundation, Novo Nordisk Foundation, Finska Läkaresällskapet, Juho Vainio Foundation, Signe and Ane Gyllenberg Foundation, University of Helsinki, Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation. Finrisk study is grateful for the THL DNA laboratory for its skillful work to produce the DNA samples used in this study and thanks the Sanger Institute and FIMM genotyping facilities for genotyping the samples. We thank the MOLGENIS team and Genomics Coordination Center of the University Medical Center Groningen for software development and data management, in particular Marieke Bijlsma and Edith Adriaanse. This work was supported by the Leenards Foundation (to Z.K.), the Swiss National Science Foundation (31003A_169929 to Z.K., Sinergia grant CRSII33-133044 to AR), Simons Foundation (SFARI274424 to AR) and SystemsX.ch (51RTP0_151019 to Z.K.). A.R.W., H.Y. and T.M.F. are supported by the European Research Council grant: 323195:SZ-245. M.A.T., M.N.W. and An.M. are supported by the Wellcome Trust Institutional Strategic Support Award (WT097835MF). For full funding information of all participating cohorts see Supplementary Note 2. Publisher Copyright: © 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85030331328&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-00556-x
DO - 10.1038/s41467-017-00556-x
M3 - Article
C2 - 28963451
AN - SCOPUS:85030331328
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 744
ER -