| Title: |
CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits |
| Authors: |
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 |
| Contributors: |
Institute for Molecular Medicine Finland; University of Helsinki; Quantitative Genetics; Complex Disease Genetics; Doctoral Programme in Biomedicine; Doctoral Programme in Population Health; University Management; Doctoral Programme in Drug Research; HUS Heart and Lung Center; Clinicum; Biosciences; Medicum; Department of Psychology and Logopedics; Helsinki Collegium for Advanced Studies; Developmental Psychology Research Group; Doctoral Programme in Clinical Research; Research Programs Unit; Research Programme of Molecular Medicine; Aarno Palotie / Principal Investigator; Genomics of Neurological and Neuropsychiatric Disorders; Doctoral Programme Brain & Mind; Department of Diagnostics and Therapeutics; Department of Medicine; Department of Public Health; Faculty of Humanities; Department of General Practice and Primary Health Care; CAMM - Research Program for Clinical and Molecular Metabolism; Johan Eriksson / Principal Investigator; Doctoral Programme in Oral Sciences |
| Publisher Information: |
Nature Publishing Group |
| Publication Year: |
2017 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
BODY-MASS INDEX; WILLIAMS-BEUREN-SYNDROME; GENOME-WIDE ASSOCIATION; DELETION SYNDROME; DEVELOPMENTAL DELAY; HUMAN HEIGHT; VARIANTS; OBESITY; SNP; MICRODUPLICATION; Biomedicine |
| Description: |
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(2)). 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 x 10(-10), 6.0 x 10(-5), and 2.9 x 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. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
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, Folkhalsan Research Foundation, Novo Nordisk Foundation, Finska Lakaresallskapet, 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.; https://hdl.handle.net/10138/227948; 85030331328; 000412052400011 |
| Availability: |
https://hdl.handle.net/10138/227948 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.A55111C6 |
| Database: |
BASE |